Sample records for zaitaku kaigo kiki
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Chen, Yi-Chuan; Huang, Pi-Chun; Woods, Andy; Spence, Charles
2016-05-27
It has been suggested that the Bouba/Kiki effect, in which meaningless speech sounds are systematically mapped onto rounded or angular shapes, reflects a universal crossmodal correspondence between audition and vision. Here, radial frequency (RF) patterns were adapted in order to compare the Bouba/Kiki effect in Eastern and Western participants demonstrating different perceptual styles. Three attributes of the RF patterns were manipulated: The frequency, amplitude, and spikiness of the sinusoidal modulations along the circumference of a circle. By testing participants in the US and Taiwan, both cultural commonalities and differences in sound-shape correspondence were revealed. RF patterns were more likely to be matched with "Kiki" than with "Bouba" when the frequency, amplitude, and spikiness increased. The responses from both groups of participants had a similar weighting on frequency; nevertheless, the North Americans had a higher weighting on amplitude, but a lower weighting on spikiness, than their Taiwanese counterparts. These novel results regarding cultural differences suggest that the Bouba/Kiki effect is partly tuned by differing perceptual experience. In addition, using the RF patterns in the Bouba/Kiki effect provides a "mid-level" linkage between visual and auditory processing, and a future understanding of sound-shape correspondences based on the mechanism of visual pattern processing.
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Phonological and orthographic influences in the bouba-kiki effect.
Cuskley, Christine; Simner, Julia; Kirby, Simon
2017-01-01
We examine a high-profile phenomenon known as the bouba-kiki effect, in which non-word names are assigned to abstract shapes in systematic ways (e.g. rounded shapes are preferentially labelled bouba over kiki). In a detailed evaluation of the literature, we show that most accounts of the effect point to predominantly or entirely iconic cross-sensory mappings between acoustic or articulatory properties of sound and shape as the mechanism underlying the effect. However, these accounts have tended to confound the acoustic or articulatory properties of non-words with another fundamental property: their written form. We compare traditional accounts of direct audio or articulatory-visual mapping with an account in which the effect is heavily influenced by matching between the shapes of graphemes and the abstract shape targets. The results of our two studies suggest that the dominant mechanism underlying the effect for literate subjects is matching based on aligning letter curvature and shape roundedness (i.e. non-words with curved letters are matched to round shapes). We show that letter curvature is strong enough to significantly influence word-shape associations even in auditory tasks, where written word forms are never presented to participants. However, we also find an additional phonological influence in that voiced sounds are preferentially linked with rounded shapes, although this arises only in a purely auditory word-shape association task. We conclude that many previous investigations of the bouba-kiki effect may not have given appropriate consideration or weight to the influence of orthography among literate subjects.
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Liang, Wenna; Li, Xihai; Chen, Houhuang; Shao, Xiang; Lin, Xuejuan; Shen, Jianying; Ding, Shanshan; Kang, Jie; Li, Candong
2016-01-01
The temporomandibular joint (TMJ), a unique synovial joint whose development differs from that of other synovial joints, develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms. The short stature homeobox 2 (Shox2) gene serves an important role in TMJ development and previous studies have demonstrated that Shox2SHOX KI/KI mice display a TMJ defective phenotype, congenital dysplasia and premature eroding of the articular disc, which is clinically defined as a TMJ disorder. In the present study, Shox2SHOX KI/KI mouse models were used to investigate the mechanisms of congenital osteoarthritis (OA)-like disease during postnatal TMJ growth. Shox2SHOX KI/KI mice were observed to develop a severe muscle wasting syndrome from day 7 postnatal. Histological examination indicated that the condyle and glenoid fossa of Shox2SHOX KI/KI mice was reduced in size in the second week after birth. The condyles of Shox2SHOX KI/KI mice exhibited reduced expression levels of collagen type II and Indian hedgehog, and increased expression of collagen type I. A marked increase in matrix metalloproteinase 9 (MMP9) and MMP13 in the condyles was also observed. These cellular and molecular defects may contribute to the observed (OA)-like phenotype of Shox2SHOX KI/KI mouse TMJs. PMID:27601064
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Eo, Taejoon; Jun, Yohan; Kim, Taeseong; Jang, Jinseong; Lee, Ho-Joon; Hwang, Dosik
2018-04-06
To demonstrate accurate MR image reconstruction from undersampled k-space data using cross-domain convolutional neural networks (CNNs) METHODS: Cross-domain CNNs consist of 3 components: (1) a deep CNN operating on the k-space (KCNN), (2) a deep CNN operating on an image domain (ICNN), and (3) an interleaved data consistency operations. These components are alternately applied, and each CNN is trained to minimize the loss between the reconstructed and corresponding fully sampled k-spaces. The final reconstructed image is obtained by forward-propagating the undersampled k-space data through the entire network. Performances of K-net (KCNN with inverse Fourier transform), I-net (ICNN with interleaved data consistency), and various combinations of the 2 different networks were tested. The test results indicated that K-net and I-net have different advantages/disadvantages in terms of tissue-structure restoration. Consequently, the combination of K-net and I-net is superior to single-domain CNNs. Three MR data sets, the T 2 fluid-attenuated inversion recovery (T 2 FLAIR) set from the Alzheimer's Disease Neuroimaging Initiative and 2 data sets acquired at our local institute (T 2 FLAIR and T 1 weighted), were used to evaluate the performance of 7 conventional reconstruction algorithms and the proposed cross-domain CNNs, which hereafter is referred to as KIKI-net. KIKI-net outperforms conventional algorithms with mean improvements of 2.29 dB in peak SNR and 0.031 in structure similarity. KIKI-net exhibits superior performance over state-of-the-art conventional algorithms in terms of restoring tissue structures and removing aliasing artifacts. The results demonstrate that KIKI-net is applicable up to a reduction factor of 3 to 4 based on variable-density Cartesian undersampling. © 2018 International Society for Magnetic Resonance in Medicine.
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Liang, Wenna; Li, Xihai; Chen, Houhuang; Shao, Xiang; Lin, Xuejuan; Shen, Jianying; Ding, Shanshan; Kang, Jie; Li, Candong
2016-10-01
The temporomandibular joint (TMJ), a unique synovial joint whose development differs from that of other synovial joints, develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms. The short stature homeobox 2 (Shox2) gene serves an important role in TMJ development and previous studies have demonstrated that Shox2SHOX KI/KI mice display a TMJ defective phenotype, congenital dysplasia and premature eroding of the articular disc, which is clinically defined as a TMJ disorder. In the present study, Shox2SHOX KI/KI mouse models were used to investigate the mechanisms of congenital osteoarthritis (OA)‑like disease during postnatal TMJ growth. Shox2SHOX KI/KI mice were observed to develop a severe muscle wasting syndrome from day 7 postnatal. Histological examination indicated that the condyle and glenoid fossa of Shox2SHOX KI/KI mice was reduced in size in the second week after birth. The condyles of Shox2SHOX KI/KI mice exhibited reduced expression levels of collagen type II and Indian hedgehog, and increased expression of collagen type I. A marked increase in matrix metalloproteinase 9 (MMP9) and MMP13 in the condyles was also observed. These cellular and molecular defects may contribute to the observed (OA)‑like phenotype of Shox2SHOX KI/KI mouse TMJs.
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A social Bouba/Kiki effect: A bias for people whose names match their faces.
Barton, David N; Halberstadt, Jamin
2018-06-01
The "bouba/kiki effect" is the robust tendency to associate rounded objects (vs. angular objects) with names that require rounding of the mouth to pronounce, and may reflect synesthesia-like mapping across perceptual modalities. Here we show for the first time a "social" bouba/kiki effect, such that experimental participants associate round names ("Bob," "Lou") with round-faced (vs. angular-faced) individuals. Moreover, consistent with a bias for expectancy-consistent information, we find that participants like targets with "matching" names, both when name-face fit is measured and when it is experimentally manipulated. Finally, we show that such bias could have important practical consequences: An analysis of voting data reveals that Senatorial candidates earn 10% more votes when their names fit their faces very well, versus very poorly. These and similar cross-modal congruencies suggest that social judgment involves not only amodal application of stored information (e.g., stereotypes) to new stimuli, but also integration of perceptual and bodily input.
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ERIC Educational Resources Information Center
Bremner, Andrew J.; Caparos, Serge; Davidoff, Jules; de Fockert, Jan; Linnell, Karina J.; Spence, Charles
2013-01-01
Western participants consistently match certain shapes with particular speech sounds, tastes, and flavours. Here we demonstrate that the "Bouba-Kiki effect", a well-known shape-sound symbolism effect commonly observed in Western participants, is also observable in the Himba of Northern Namibia, a remote population with little exposure to…
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Dental abnormalities in a mouse model for craniometaphyseal dysplasia.
Dutra, E H; Chen, I-P; Reichenberger, E J
2013-02-01
Mice carrying a knock-in mutation (Phe377del) in the Ank gene replicate many skeletal characteristics of human craniometaphyseal dysplasia, including hyperostotic mandibles. Ank (KI/KI) mice have normal morphology of erupted molars and incisors but excessive cementum deposition with increased numbers of Ibsp- and Dmp1-positive cells on root surfaces. The cervical loops of adult Ank (KI/KI) lower incisors are at the level of the third molars, while they are close to the mandibular foramen in Ank (+/+) mice. Furthermore, Ank (KI/KI) incisors show decreased eruption rates, decreased proliferation of odontoblast precursors, and increased cell apoptosis in the stellate reticulum. However, their capability for continuous elongation is not compromised. Quantification of TRAP-positive cells in the apical ends of Ank (KI/KI) incisors revealed decreased osteoclast numbers and osteoclast surfaces. Bisphosphonate injections in Ank (+/+) mice replicate the Ank (KI/KI) incisor phenotype. These results and a comparison with the dental phenotype of Ank loss-of-function mouse models suggest that increased cementum thickness may be caused by decreased extracellular PPi levels and that the incisor phenotype is likely due to hyperostosis of mandibles, which distinguishes Ank (KI/KI) mice from the other Ank mouse models.
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Li, Yan; Yu, Shirley; Duncan, Todd; Li, Yichao; Liu, Pinghu; Gene, Erelda; Cortes-Pena, Yoel; Qian, Haohua; Dong, Lijin; Redmond, T Michael
2015-08-01
Human RPE65 mutations cause a spectrum of blinding retinal dystrophies from severe early-onset disease to milder manifestations. The RPE65 P25L missense mutation, though having <10% of wild-type (WT) activity, causes relatively mild retinal degeneration. To better understand these mild forms of RPE65-related retinal degeneration, and their effect on cone photoreceptor survival, we generated an Rpe65/P25L knock-in (KI/KI) mouse model. We found that, when subject to the low-light regime (∼100 lux) of regular mouse housing, homozygous Rpe65/P25L KI/KI mice are morphologically and functionally very similar to WT siblings. While mutant protein expression is decreased by over 80%, KI/KI mice retinae retain comparable 11-cis-retinal levels with WT. Consistently, the scotopic and photopic electroretinographic (ERG) responses to single-flash stimuli also show no difference between KI/KI and WT mice. However, the recovery of a-wave response following moderate visual pigment bleach is delayed in KI/KI mice. Importantly, KI/KI mice show significantly increased resistance to high-intensity (20 000 lux for 30 min) light-induced retinal damage (LIRD) as compared with WT, indicating impaired rhodopsin regeneration in KI/KI. Taken together, the Rpe65/P25L mutant produces sufficient chromophore under normal conditions to keep opsins replete and thus manifests a minimal phenotype. Only when exposed to intensive light is this hypomorphic mutation manifested physiologically, as its reduced expression and catalytic activity protects against the successive cycles of opsin regeneration underlying LIRD. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Kittaka, Mizuho; Mayahara, Kotoe; Mukai, Tomoyuki; Yoshimoto, Tetsuya; Yoshitaka, Teruhito; Gorski, Jeffrey P; Ueki, Yasuyoshi
2018-01-01
Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP+) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2 KI/KI ) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2 KI/KI mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old. Levels of serum collagen I C-terminal telopeptide (ICTP), a marker of bone resorption generated by matrix metalloproteinases (MMPs), were elevated, whereas levels of serum cross-linked C-telopeptide (CTX), another resorption marker produced by cathepsin K, were not increased. Collagenolytic MMP levels were increased in the inflamed joints of the Sh3bp2 KI/KI mice deficient in c-Fos. Resorption pits contained a large number of F4/80+ macrophages and genetic depletion of macrophages rescued these erosive changes. Importantly, administration of NSC405020, an MMP14 inhibitor targeted to the hemopexin (PEX) domain, suppressed bone erosion in c-Fos-deficient Sh3bp2 KI/KI mice. After activation of the NF-κB pathway, macrophage colony-stimulating factor (M-CSF)-dependent macrophages from c-Fos-deficient Sh3bp2 KI/KI mice expressed increased amounts of MMP14 compared with wild-type macrophages. Interestingly, receptor activator of NF-κB ligand (RANKL)-deficient Sh3bp2 KI/KI mice failed to show notable bone erosion, whereas c-Fos deletion did restore bone erosion to the RANKL-deficient Sh3bp2 KI/KI mice, suggesting that osteolytic transformation of macrophages requires both loss-of-function of c-Fos and gain-of-function of SH3BP2 in this model. These data provide the first genetic evidence that cells other than osteoclasts can cause focal bone destruction in
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Early sound symbolism for vowel sounds.
Spector, Ferrinne; Maurer, Daphne
2013-01-01
Children and adults consistently match some words (e.g., kiki) to jagged shapes and other words (e.g., bouba) to rounded shapes, providing evidence for non-arbitrary sound-shape mapping. In this study, we investigated the influence of vowels on sound-shape matching in toddlers, using four contrasting pairs of nonsense words differing in vowel sound (/i/ as in feet vs. /o/ as in boat) and four rounded-jagged shape pairs. Crucially, we used reduplicated syllables (e.g., kiki vs. koko) rather than confounding vowel sound with consonant context and syllable variability (e.g., kiki vs. bouba). Toddlers consistently matched words with /o/ to rounded shapes and words with /i/ to jagged shapes (p < 0.01). The results suggest that there may be naturally biased correspondences between vowel sound and shape.
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Early sound symbolism for vowel sounds
Spector, Ferrinne; Maurer, Daphne
2013-01-01
Children and adults consistently match some words (e.g., kiki) to jagged shapes and other words (e.g., bouba) to rounded shapes, providing evidence for non-arbitrary sound–shape mapping. In this study, we investigated the influence of vowels on sound–shape matching in toddlers, using four contrasting pairs of nonsense words differing in vowel sound (/i/ as in feet vs. /o/ as in boat) and four rounded–jagged shape pairs. Crucially, we used reduplicated syllables (e.g., kiki vs. koko) rather than confounding vowel sound with consonant context and syllable variability (e.g., kiki vs. bouba). Toddlers consistently matched words with /o/ to rounded shapes and words with /i/ to jagged shapes (p < 0.01). The results suggest that there may be naturally biased correspondences between vowel sound and shape. PMID:24349684
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Nakamura, Haruko; Takahashi-Jitsuki, Aoi; Makihara, Hiroko; Asano, Tetsuya; Kimura, Yayoi; Nakabayashi, Jun; Yamashita, Naoya; Kawamoto, Yuko; Nakamura, Fumio; Ohshima, Toshio; Hirano, Hisashi; Tanaka, Fumiaki; Goshima, Yoshio
2018-05-11
CRMP2, alternatively designated as DPYSL2, was the first CRMP family member to be identified as an intracellular molecule mediating the signaling of the axon guidance molecule Semaphorin 3A (Sema3A). In Sema3A signaling, cyclin-dependent kinase 5 (Cdk5) primarily phosphorylates CRMP2 at Ser522. Glycogen synthase kinase-3β (GSK-3β) subsequently phosphorylates the residues of Thr509 and Thr514 of CRMP2. Previous studies showed that CRMP2 is involved in pathogenesis of neurological disorders such as Alzheimer's disease. In Alzheimer's disease, hyper-phosphorylated forms of CRMP2 are accumulated in the paired helical filaments. To get insight into the possible involvement of the phosphorylation of CRMP2 in pathogenesis of neurological disorders, we previously created CRMP2 S522A knock-in (crmp2 ki/ki ) mice and demonstrated that the phosphorylation of CRMP2 at Ser522 is involved in normal dendrite patterning in cortical neurons. However, the behavioral impact and in vivo signaling network of the CRMP2 phosphorylation are not fully understood. In this study, we performed behavioral and proteomics analysis of crmp2 ki/ki mice. The crmp2 ki/ki mice appeared healthy and showed no obvious differences in physical characteristics compared to wild-type mice, but they showed impaired emotional behavior, reduced sociality, and low sensitivity to pain stimulation. Through mass-spectrometry-based proteomic analysis, we found that 59 proteins were increased and 77 proteins were decreased in the prefrontal cortex of crmp2 ki/ki mice. Notably, CRMP3, CRMP4, and CRMP5, the other CRMP family proteins, were increased in crmp2 ki/ki mice. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses identified 14 pathways in increased total proteins and 13 pathways in decreased total proteins which are associated with the pathogenesis of Parkinson's, Alzheimer's, and Huntington's diseases. We also detected 20 pathways in increased phosphopeptides and 16 pathways in decreased
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Etzi, Roberta; Spence, Charles; Zampini, Massimiliano; Gallace, Alberto
2016-01-01
Over the last decade, scientists working on the topic of multisensory integration, as well as designers and marketers involved in trying to understand consumer behavior, have become increasingly interested in the non-arbitrary associations (e.g., sound symbolism) between different sensorial attributes of the stimuli they work with. Nevertheless, to date, little research in this area has investigated the presence of these crossmodal correspondences in the tactile evaluation of everyday materials. Here, we explore the presence and nature of the associations between tactile sensations, the sound of non-words, and people's emotional states. Samples of cotton, satin, tinfoil, sandpaper, and abrasive sponge, were stroked along the participants' forearm at the speed of 5 cm/s. Participants evaluated the materials along several dimensions, comprising scales anchored by pairs of non-words (e.g., Kiki/Bouba) and adjectives (e.g., ugly/beautiful). The results revealed that smoother textures were associated with non-words made up of round-shaped sounds (e.g., Maluma), whereas rougher textures were more strongly associated with sharp-transient sounds (e.g., Takete). The results also revealed the presence of a number of correspondences between tactile surfaces and adjectives related to visual and auditory attributes. For example, smooth textures were associated with features evoked by words such as 'bright' and 'quiet'; by contrast, the rougher textures were associated with adjectives such as 'dim' and 'loud'. The textures were also found to be associated with a number of emotional labels. Taken together, these results further our understanding of crossmodal correspondences involving the tactile modality and provide interesting insights in the applied field of design and marketing.
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Isono, Toshinari; Yamashita, Naoya; Obara, Masami; Araki, Tomomi; Nakamura, Fumio; Kamiya, Yoshinori; Alkam, Tursun; Nitta, Atsumi; Nabeshima, Toshitaka; Mikoshiba, Katsuhiko; Ohshima, Toshio; Goshima, Yoshio
2013-11-01
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) protein and tau deposition in the brain. Numerous studies have reported a central role of Aβ in the development of AD, but the pathogenesis is not well understood. Collapsin response mediator protein 2 (CRMP2), an intracellular protein mediating a repulsive axon guidance molecule, Semaphorin3A, is also accumulated in neurofibrillary tangles in AD brains. To gain insight into the role of CRMP2 phosphorylation in AD pathogenesis, we investigated the effects of Aβ neurotoxicity in CRMP2 phosphorylation-deficient knock-in (crmp2(ki/ki)) mice, in which the serine residue at 522 was replaced with alanine. Intracerebroventricular (i.c.v.) injection of Aβ₂₅₋₃₅ peptide, a neurotoxic fragment of Aβ protein, to wild-type (wt) mice increased hippocampal phosphorylation of CRMP2. Behavioral assessment revealed that i.c.v. injection of Aβ₂₅₋₃₅ peptide caused impairment of novel object recognition in wt mice, while the same peptide did not in crmp2(ki/ki) mice. In electrophysiological recording, wt and crmp2(ki/ki) mice have similar input-output basal synaptic transmission and paired-pulse ratios. However, long-term potentiation was impaired in hippocampal slices of Aβ₂₅₋₃₅ peptide-treated wt but not those of crmp2(ki/ki). Our findings indicate that CRMP2 phosphorylation is required for Aβ-induced impairment of cognitive memory and synaptic plasticity. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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What's in a Name? Sound Symbolism and Gender in First Names.
Sidhu, David M; Pexman, Penny M
2015-01-01
Although the arbitrariness of language has been considered one of its defining features, studies have demonstrated that certain phonemes tend to be associated with certain kinds of meaning. A well-known example is the Bouba/Kiki effect, in which nonwords like bouba are associated with round shapes while nonwords like kiki are associated with sharp shapes. These sound symbolic associations have thus far been limited to nonwords. Here we tested whether or not the Bouba/Kiki effect extends to existing lexical stimuli; in particular, real first names. We found that the roundness/sharpness of the phonemes in first names impacted whether the names were associated with round or sharp shapes in the form of character silhouettes (Experiments 1a and 1b). We also observed an association between femaleness and round shapes, and maleness and sharp shapes. We next investigated whether this association would extend to the features of language and found the proportion of round-sounding phonemes was related to name gender (Analysis of Category Norms). Finally, we investigated whether sound symbolic associations for first names would be observed for other abstract properties; in particular, personality traits (Experiment 2). We found that adjectives previously judged to be either descriptive of a figuratively 'round' or a 'sharp' personality were associated with names containing either round- or sharp-sounding phonemes, respectively. These results demonstrate that sound symbolic associations extend to existing lexical stimuli, providing a new example of non-arbitrary mappings between form and meaning.
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What’s in a Name? Sound Symbolism and Gender in First Names
2015-01-01
Although the arbitrariness of language has been considered one of its defining features, studies have demonstrated that certain phonemes tend to be associated with certain kinds of meaning. A well-known example is the Bouba/Kiki effect, in which nonwords like bouba are associated with round shapes while nonwords like kiki are associated with sharp shapes. These sound symbolic associations have thus far been limited to nonwords. Here we tested whether or not the Bouba/Kiki effect extends to existing lexical stimuli; in particular, real first names. We found that the roundness/sharpness of the phonemes in first names impacted whether the names were associated with round or sharp shapes in the form of character silhouettes (Experiments 1a and 1b). We also observed an association between femaleness and round shapes, and maleness and sharp shapes. We next investigated whether this association would extend to the features of language and found the proportion of round-sounding phonemes was related to name gender (Analysis of Category Norms). Finally, we investigated whether sound symbolic associations for first names would be observed for other abstract properties; in particular, personality traits (Experiment 2). We found that adjectives previously judged to be either descriptive of a figuratively ‘round’ or a ‘sharp’ personality were associated with names containing either round- or sharp-sounding phonemes, respectively. These results demonstrate that sound symbolic associations extend to existing lexical stimuli, providing a new example of non-arbitrary mappings between form and meaning. PMID:26016856
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The Interactive Origin of Iconicity
ERIC Educational Resources Information Center
Tamariz, Mónica; Roberts, Seán G.; Martínez, J. Isidro; Santiago, Julio
2018-01-01
We investigate the emergence of iconicity, specifically a bouba-kiki effect in miniature artificial languages under different functional constraints: when the languages are reproduced and when they are used communicatively. We ran transmission chains of (a) participant dyads who played an interactive communicative game and (b) individual…
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Sound Symbolism in Infancy: Evidence for Sound-Shape Cross-Modal Correspondences in 4-Month-Olds
ERIC Educational Resources Information Center
Ozturk, Ozge; Krehm, Madelaine; Vouloumanos, Athena
2013-01-01
Perceptual experiences in one modality are often dependent on activity from other sensory modalities. These cross-modal correspondences are also evident in language. Adults and toddlers spontaneously and consistently map particular words (e.g., "kiki") to particular shapes (e.g., angular shapes). However, the origins of these systematic mappings…
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Shaking Takete and Flowing Maluma. Non-Sense Words Are Associated with Motion Patterns
Koppensteiner, Markus; Stephan, Pia; Jäschke, Johannes Paul Michael
2016-01-01
People assign the artificial words takete and kiki to spiky, angular figures and the artificial words maluma and bouba to rounded figures. We examined whether such a cross-modal correspondence could also be found for human body motion. We transferred the body movements of speakers onto two-dimensional coordinates and created animated stick-figures based on this data. Then we invited people to judge these stimuli using the words takete-maluma, bouba-kiki, and several verbal descriptors that served as measures of angularity/smoothness. In addition to this we extracted the quantity of motion, the velocity of motion and the average angle between motion vectors from the coordinate data. Judgments of takete (and kiki) were related to verbal descriptors of angularity, a high quantity of motion, high velocity and sharper angles. Judgments of maluma (or bouba) were related to smooth movements, a low velocity, a lower quantity of motion and blunter angles. A forced-choice experiment during which we presented subsets with low and high rankers on our motion measures revealed that people preferably assigned stimuli displaying fast movements with sharp angles in motion vectors to takete and stimuli displaying slow movements with blunter angles in motion vectors to maluma. Results indicated that body movements share features with information inherent in words such as takete and maluma and that people perceive the body movements of speakers on the level of changes in motion direction (e.g., body moves to the left and then back to the right). Follow-up studies are needed to clarify whether impressions of angularity and smoothness have similar communicative values across different modalities and how this affects social judgments and person perception. PMID:26939013
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The Implementation of Special Autonomy in West Papua, Indonesia: Problems and Recommendations
2006-12-01
ONLY (Leave blank) 2. REPORT DATE December 2006 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE : The Implementations...done without all their support and the support from my thesis editor, Lee Rappold, who excellently enhanced the grammatical and structural English... prayers , and understanding; and also to my children, Kiky and Intan, who without “objection” understood that I had a thesis that had to be done. This
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Oberman, Lindsay M; Ramachandran, Vilayanur S
2008-01-01
Autism is a complex disorder, characterized by social, cognitive, communicative, and motor symptoms. One suggestion, proposed in the current study, to explain the spectrum of symptoms is an underlying impairment in multisensory integration (MSI) systems such as a mirror neuron-like system. The mirror neuron system, thought to play a critical role in skills such as imitation, empathy, and language can be thought of as a multisensory system, converting sensory stimuli into motor representations. Consistent with this, we report preliminary evidence for deficits in a task thought to tap into MSI--"the bouba-kiki task" in children with ASD. The bouba-kiki effect is produced when subjects are asked to pair nonsense shapes with nonsense "words". We found that neurotypical children chose the nonsense "word" whose phonemic structure corresponded with the visual shape of the stimuli 88% of the time. This is presumably because of mirror neuron-like multisensory systems that integrate the visual shape with the corresponding motor gestures used to pronounce the nonsense word. Surprisingly, individuals with ASD only chose the corresponding name 56% of the time. The poor performance by the ASD group on this task suggests a deficit in MSI, perhaps related to impaired MSI brain systems. Though this is a behavioral study, it provides a testable hypothesis for the communication impairments in children with ASD that implicates a specific neural system and fits well with the current findings suggesting an impairment in the mirror systems in individuals with ASD.
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50th anniversary of the inauguration of John F. Kennedy
2011-01-20
NASA Administrator Charles Bolden. 3rd from left, introduces Edward Moore Kennedy III, 4th from left, to NASA Astronaut Leland Melvin, left, and former NASA Astronaut Scott Altman, 2nd from left, as Edward's mother Kiki Kennedy, wife of Edward M Kennedy Jr. and NASA Deputy Administrator Lori Garver, right, look on at an event recognizing the 50th anniversary of the inauguration of John F. Kennedy as president of the United States, Thursday, Jan. 20, 2001 at the U.S. Capitol rotunda. Photo Credit: (NASA/Bill Ingalls)
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Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome
Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A
2017-01-01
Abstract Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential ‘rapamycin metabolic signature.’ These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. PMID:28973153
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Tsukada, Noriko; Saito, Yasuhiko
2006-01-01
were still many older Japanese people who felt reluctant about using either type of care service. But it is expected that the quality of services under Kaigo Hoken (the mandatory public long-term care social insurance system) will improve further and that older people's attitudes toward service utilization will change for the better. In the meantime, professional service providers will have to be sensitive to older people's perceptions about service utilization if they would like to continue to contribute to the improvement process of Kaigo Hoken as a positive force.
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Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.
Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A
2017-12-01
Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential 'rapamycin metabolic signature.' These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.
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The behavior of groundwater with dispersion in coastal aquifers
NASA Astrophysics Data System (ADS)
Kakinuma, Tadao; Kishi, Yosuke; Inouchi, Kunimitsu
1988-04-01
A three-dimensional steady-state hydrodynamic dispersion model is used to simulate seawater encroachment in the confined aquifers in the estuaries of the Naka and Kiki Rivers in Japan. Two expressions of the dispersion coefficient are considered; one is constant over the entire region of the aquifer and the other is dependent on the flow velocity of the groundwater. The magnitudes of the constant dispersion coefficients in the horizontal and vertical directions, Dxx and Dzz, as well as the longitudinal and lateral dispersivities, aL and aT, are determined so as to reproduce the regional distributions of salt concentration in the confined aquifers in both estuaries. It is found that Dxx = 5 cm 2s -1, Dzz = 5-0.5 cm 2s -1 and aL = 1000-1250 m, aT = 100-125 m in the estuary of the Naka River; and Dxx = 0.2 cm 2s -1, Dzz = 0.2-0.02 cm 2s -1 and aL = 200 m, aT = 200-20 m in the estuary of the Kiki River. Examining the local distributions of the dispersion coefficient computed from the dispersivity and velocity fields of groundwater in both estuaries, the same value as estimated in the analysis with the constant dispersion coefficient is located in the middle layer of the aquifer. In the estuary of the Naka River, the piezometric surface predicted with the dispersion model with the velocity-dependent dispersion coefficient is almost the same as that predicted with the dispersion model with the constant dispersion coefficient and they are 5 10% lower than that predicted with the interface model (Kakinuma et al., 1984). They are, however, about 1.3 times the observed one.
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Kim, Yeon-Pyo; Kim, Sun; Joh, Ju-Youn; Hwang, Hwan-Sik
2014-05-01
To examine the effects of interaction between dynapenic component of the European Working Group on Sarcopenia in Older People (EWGSOP) sarcopenia and obesity (dynapenia × obesity) on activities of daily living (ADL) in older participants. Cross-sectional analysis of the Validity and Reliability of Korean Frailty Index and the Validity and Reliability of the Kaigo-Yobo Checklist in Korean Elderly studies. Six welfare facilities operated by government in South Korea. Four hundred eighty-seven community-dwelling individuals (157 males, 330 females) >65 years of age. Dynapenic component of the EWGSOP sarcopenia was defined as usual gait speed <0.8 m/s or grip strength lower than cut-off value (male <25.3 kg, female <12.0 kg). Obesity was defined as body mass index ≥27.5 kg/m(2). ADL were assessed using the Barthel index. There were 14 obese with dynapenic component cases (2 males, 12 females) of the 487 participants. Interaction of dynapenia and obesity was significant on multivariate generalized linear model analysis (P = .015). Dynapenic component of the EWGSOP sarcopenia and obesity in the elderly is associated with multiplicative interactions rather than additive interactions in ADL. Copyright © 2014 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.
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2009-09-01
resulting equations is given below: 1. Electron Density Fluctuation Amplitude e eb eoe oeceeoe e oee m Tk iUk iUk k iUk m e nn...3. Axial Electron Velocity Fluctuation Amplitude kikiUk iUk n nm Tk m e U cezeoe ceeoe e oee eb e ez , 2 2...kiUkki iUk n nm Tk m e U eoezce ceeoe e oee eb e e , 2 2 , , ~~ ~ (15) 5. Axial Ion Velocity
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1998-09-02
(Left to right) STS-95 Payload Specialists John H. Glenn Jr., senator from Ohio, and Chiaki Mukai, with the National Space Development Agency of Japan, talk with Kiki Chaput, trainer, United Space Alliance-Houston, during the Crew Equipment Interface Test (CEIT) for their mission. The CEIT gives astronauts an opportunity for a hands-on look at the payloads on whcih they will be working on orbit. The launch of the STS-95 mission, aboard Space Shuttle Discovery, is scheduled for Oct. 29, 1998. The mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process
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Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy.
Shchors, Ksenya; Persson, Anders I; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S; Hanahan, Douglas; Weiss, William A; Evan, Gerard I
2013-04-16
Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRas(V12) mouse model crossed into the p53ER(TAM) background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ER(TAM) allele. The p53ER(TAM) protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRas(V12);p53(+/KI) mice abrogate the p53 pathway by mutating p19(ARF)/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ER(TAM) allele. By contrast, gliomas arising in GFAP-HRas(V12);p53(KI/KI) mice develop in the absence of functional p53. Such tumors retain a functional p19(ARF)/MDM2-signaling pathway, and restoration of p53ER(TAM) allele triggers p53-tumor-suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14(ARF)/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRas(V12);p53(KI/KI) animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ER(TAM) activity mitigated the selective pressure to inactivate the p19(ARF)/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance.
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Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy
Shchors, Ksenya; Persson, Anders I.; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S.; Hanahan, Douglas; Weiss, William A.; Evan, Gerard I.
2013-01-01
Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRasV12 mouse model crossed into the p53ERTAM background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ERTAM allele. The p53ERTAM protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRasV12;p53+/KI mice abrogate the p53 pathway by mutating p19ARF/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ERTAM allele. By contrast, gliomas arising in GFAP-HRasV12;p53KI/KI mice develop in the absence of functional p53. Such tumors retain a functional p19ARF/MDM2-signaling pathway, and restoration of p53ERTAM allele triggers p53-tumor–suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14ARF/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRasV12;p53KI/KI animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ERTAM activity mitigated the selective pressure to inactivate the p19ARF/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance. PMID:23542378
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Styles, Suzy J; Gawne, Lauren
2017-01-01
Eighty-seven years ago, Köhler reported that the majority of students picked the same answer in a quiz: Which novel word form ('maluma' or 'takete') went best with which abstract line drawing (one curved, one angular). Others have consistently shown the effect in a variety of contexts, with only one reported failure by Rogers and Ross. In the spirit of transparency, we report our own failure in the same journal. In our study, speakers of Syuba, from the Himalaya in Nepal, do not show a preference when matching word forms 'kiki' and 'bubu' to spiky versus curvy shapes. We conducted a meta-analysis of previous studies to investigate the relationship between pseudoword legality and task effects. Our combined analyses suggest a common source for both of the failures: 'wordiness' - We believe these tests fail when the test words do not behave according to the sound structure of the target language.
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A resolution honoring the life and service of Enrique "Kiki" Camarena.
Sen. Feinstein, Dianne [D-CA
2010-03-04
Senate - 03/04/2010 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:
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[Role of Visiting Nursing Care in Japanese Home Healthcare].
Yu, Sang-Ju
2018-02-01
Taiwan's rapidly aging society is expected to make it a super-aged society in 2026. By 2060, people aged 65 or older will account for 40% of the population, a ratio that will approximate that in Japan. In Japan, the elderly population was 27.3% in 2016. By 2025, when the baby-boomers become 75 years old in Japan, issues of long-term care and end-of-life care will be more important and challenging. Since 1976, more Japanese have died in hospital settings than in home settings. Although the percentage of people dying at home increased slightly to 12.7% in 2016, after the recent introduction and promotion of home healthcare, Japan will face a significant challenge to deal with the healthcare 'tsunami' of high natural death rates, which is expected to impose a heavy death burdened on society by 2040, when the death rate is expected to reach 1,670,000/year. Therefore, the Japanese authorities have begun to promote the Community-based Integrated Care System, in which home healthcare and visiting nursing play crucial roles. This article summarizes the historical trend and current situation of visiting nursing in Japan. Japan uses a hybrid payment system for visiting nursing that is financially supported both through private medical insurance policies and Kaigo insurance (Japanese long-term care insurance). The total of 8613 visiting nursing stations that were active in community settings in 2016 cooperated with 14,000 support clinics for home healthcare and cared for 570,000 patients in home settings. We believe that visiting nursing will play an important role in home healthcare in Taiwan in the future.
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NASA Astrophysics Data System (ADS)
Zhang, Qi; Kosaka, Michitaka; Shirahada, Kunio; Yabutani, Takashi
This paper proposes a new framework for B to B collaboration process based on a concept of service. Service value, which gives users satisfaction for provided services, depends on the situation, user characteristics, and user objectives in seeking the service. Vargo proposed Service Dominant Logic (SDL), which determines service value according to “value in use”. This concept illustrates the importance of the relationship between the service itself and its situation. This relationship is analogous to electro-magnetic field theory in physics. We developed the concept of service fields to create service value based on an analogy of the electro-magnetic field. By applying this concept to B to B collaboration, a model of service value co-creation in the collaboration can be formulated. Then, the collaboration can be described by 4 steps of KIKI model (Knowledge sharing related to service system, Identification of service field, Knowledge creation for new service idea, Implementation of service idea). As its application to B to B collaboration, the energy saving service business is reported to demonstrate the validity of the proposed collaboration model. This concept can be applied to make a collaboration process effective.
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ERIC Educational Resources Information Center
Carey, A'Keitha
2016-01-01
I discuss my journey in the construction, pedagogy, and philosophy of the dance technique CaribFunk™. CaribFunk fuses Afro-Caribbean (traditional and social dance), classical ballet, modern, and fitness elements. It also encourages exploration of self while investigating identity, citizenship, and culture through a kinesthetic expression of the…
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Nesci, Salvatore; Ventrella, Vittoria; Trombetti, Fabiana; Pirini, Maurizio; Borgatti, Anna Rosa; Pagliarani, Alessandra
2011-02-01
Tri-n-butyltin (TBT) has long been considered as the most toxic among organotins, especially to membrane systems. The partially dealkylated derivative di-n-butyltin (DBT) has up to now received poor attention and, whenever considered, shown to be less toxic than TBT except on the immune system. The present kinetic approach evidences that both TBT and DBT in vitro inhibit the Mg-ATPase in mussel digestive gland mitochondria by a different mechanism. DBT even displays a higher efficiency than TBT (IC(50)=0.32 μM for TBT vs. 0.19 μM for DBT) in inhibiting the enzyme hydrolytic activity. Differently from TBT which at high concentrations (>1 μM) apparently decreases the oligomycin-sensitivity of the Mg-ATPase, DBT at any concentration tested does not affect the oligomycin sensitivity. TBT probably binds to F(0), either in the form of free enzyme or of enzyme-substrate complex (Ki=K'i), acting as non-competitive inhibitor with respect to the ATP substrate. Conversely DBT, which acts as uncompetitive inhibitor of ATP and as competitive inhibitor of Mg(2+) cofactor, may bind strongly to F(1) subunit, thus preventing ATP hydrolysis. The Mg-ATPase inhibition by both organotins warns against a potential threat to crucial cell energy metabolism processes even after years from contamination and partial TBT debutylation. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells.
Penha, Ricardo Cortez Cardoso; Pellecchia, Simona; Pacelli, Roberto; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo
2018-03-01
Ionizing radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, this study investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2), as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized, and data were confirmed by quantitative real-time polymerase chain reaction evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p, and rno-miR-541-5p in irradiated cells. The miR-199a-3p and miR-10b-5p targets were validated by quantitative real-time polymerase chain reaction, Western blot, and luciferase target assays. The effects of miR-199a-3p and miR-10b-5p on DNA repair were determined by evaluating the activation of the protein kinases ataxia-telangiectasia mutated, ataxia telangiectasia, and Rad3-related and the serine 39 phosphorylation of variant histone H2AX as an indirect measure of double-strand DNA breaks in irradiated FRTL-5 CL2 cells. The impact of miR-10b-5p on radiosensitivity was analyzed by cell counting and MTT assays in FRTL-5 CL2, Kras-transformed FRTL-5 CL2 (FRTL KiKi), and 8505c cell lines. The results reveal that miR-10b-5p and miR-199a-3p display the most pronounced alterations in expression in irradiated FRTL-5 CL2 cells. Dicer1 and Lin28b were validated as targets of miR-10b-5p and miR-199a-3p, respectively. Functional studies demonstrate that miR-10b-5p increases the growth rate of FRTL-5 CL2 cells, while miR-199a-3p inhibits their proliferation. Moreover, both of these microRNAs negatively affect homologous recombination repair, reducing activated ataxia-telangiectasia mutated and Rad3-related protein levels
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Kollock, Ronny; Rost, Katharina; Batke, Monika; Glatt, Hansruedi
2009-12-15
Pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DCNP), potent inhibitors of phenol sulphotransferases, are frequently used in animal studies to elucidate the role of these enzymes in the biotransformation and toxicity of xenobiotics. An unexpected finding with 1-hydroxymethylpyrene--a strong decrease in the excretion of the corresponding carboxylic acid in rats concurrently treated with PCP-led us to suspect that this sulphotransferase inhibitor may also affect alcohol dehydrogenases (ADHs) and/or aldehyde dehydrogenases (ALDHs). Subsequently we investigated the influence of PCP and DCNP on the activity of cDNA-expressed human ADHs and ALDHs. PCP inhibited all four ADHs studied. The inhibition was strong for ADH3 (K(i) 1.4 microM, K(i)' 5.2 microM, mixed-type) and ADH2 (K(i) 3.7 microM, competitive), but moderate for ADH4 (K(i) 81 microM, competitive) and ADH1C (K(i)' 310 microM, uncompetitive). Activities of ALDH2 and ALDH3A1 were unaffected by PCP (used up to a concentration of 1 mM). In contrast, DCNP primarily inhibited ALDH2 (K(i)=K(i)' 7.4 microM, non-competitive), showed moderate competitive inhibition of ADH2 (K(i) 160 microM) and ADH4 (K(i) 710 microM), but did not affect the remaining enzymes (ADH1C, ADH3 and ALDH3A1). The study demonstrates that caution is required when using putative specific enzyme inhibitors in biotransformation studies.
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Gilmore, Brendan F; Carson, Louise; McShane, Laura L; Quinn, Derek; Coulter, Wilson A; Walker, Brian
2006-08-18
In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.
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Manuylov, Nikolay L.; Fujiwara, Yuko; Adameyko, Igor I.; Poulat, Francis
2007-01-01
We have previously established an in vivo requirement for GATA4 and FOG2 transcription factors in sexual differentiation. Fog2 null mouse fetuses or fetuses homozygous for a targeted mutation in Gata4 (Gata4ki), which cripples the GATA4-FOG2 interaction, exhibit a profound and early block in testis differentiation in both sexes. Others have shown that XX mice with the Ods transgenic insertion or the Wt1-Sox9 YAC transgene overexpress the testis differentiation gene, Sox9. Thus, these XX animals undergo dominant sex-reversal by developing into phenotypically normal, but sterile, males. Now we have determined that Fog2 haploinsufficiency prevents (suppresses) this dominant sex-reversal and Fog2+/− Wt1-Sox9 or Ods XX animals develop normally - as fertile females. The suppression of sex-reversal in Fog2 heterozygous females results from approximately 50% downregulation of the expression from the transgene-associated allele of Sox9. The GATA4/FOG2-dependent sex reversal observed in the transgenic XX gonads has to rely on gene targets other than the Y chromosome-linked Sry gene. Importantly, Fog2 null or Gata4ki/ki embryos (either XX or XY) fail to express detectable levels of Sox9 despite carrying the Ods mutation or Wt1-Sox9 transgene. Fog2 haploinsufficiency leads to a decreased amount of SOX9-positive cells in XY gonads. We conclude that FOG2 is a limiting factor in the formation of a functional GATA4/FOG2 transcription complex that is required for Sox9 expression during gonadogenesis. PMID:17540364
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Quantitative assessment of computational models for retinotopic map formation
Sterratt, David C; Cutts, Catherine S; Willshaw, David J; Eglen, Stephen J
2014-01-01
ABSTRACT Molecular and activity‐based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity‐based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2‐EphA3 ki/ki, Isl2‐EphA3 ki/+, ephrin‐A2,A3,A5 triple knock‐out (TKO), and Math5 −/− (Atoh7). Two models successfully reproduced the extent of the Math5 −/− anteromedial projection, but only one of those could account for the collapse point in Isl2‐EphA3 ki/+. The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin‐A2,A3,A5 TKO phenotype, suggesting either an incomplete knock‐out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 641–666, 2015 PMID:25367067
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Reichenbach, Myriam; Lim, Tiongti; Reichenbach, Horst-Dieter; Guengoer, Tuna; Habermann, Felix A; Matthiesen, Marieke; Hofmann, Andreas; Weber, Frank; Zerbe, Holm; Grupp, Thomas; Sinowatz, Fred; Pfeifer, Alexander; Wolf, Eckhard
2010-08-01
Lentiviral vectors are a powerful tool for the genetic modification of livestock species. We previously generated transgenic founder cattle with lentiviral integrants carrying enhanced green fluorescent protein (EGFP) under the control of the phosphoglycerate kinase (PGK) promoter. In this study, we investigated the transmission of LV-PGK-EGFP integrants through the female and male germ line in cattle. A transgenic founder heifer (#562, Kiki) was subjected to superovulation treatment and inseminated with semen from a non-transgenic bull. Embryos were recovered and transferred to synchronized recipient heifers, resulting in the birth of a healthy male transgenic calf expressing EGFP as detected by in vivo imaging. Semen from a transgenic founder bull (#561, Jojo) was used for in vitro fertilization (IVF) of in vitro matured (IVM) oocytes from non-transgenic cows. The rates of cleavage and development to blastocyst in vitro corresponded to 52.0 +/- 4.1 and 24.5 +/- 4.4%, respectively. Expression of EGFP was observed at blastocyst stage (day 7 after IVF) and was seen in 93.0% (281/302) of the embryos. 24 EGFP-expressing embryos were transferred to 9 synchronized recipients. Analysis of 2 embryos, flushed from the uterus on day 15, two fetuses recovered on day 45, and a healthy male transgenic calf revealed consistent high-level expression of EGFP in all tissues investigated. Our study shows for the first time transmission of lentiviral integrants through the germ line of female and male transgenic founder cattle. The pattern of inheritance was consistent with Mendelian rules. Importantly, high fidelity expression of EGFP in embryos, fetuses, and offspring of founder #561 provides interesting tools for developmental studies in cattle, including interactions of gametes, embryos and fetuses with their maternal environment.
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Yoshiyuki, Noriko; Kono, Ayumi; Soga, Tomoko; Kanaya, Yukiko; Hotta, Kuniko
2016-01-01
This cross-sectional study clarified the association between service utilization patterns and frailty in the elderly certified at the support level in Japan's long-term care insurance (LTCI) system. We analyzed 710 subjects who completed in-home assessments and interviews from 1,033 elderly aged 65 and over living in Izumiotsu who had been certified at the LTCI support level in August 2014. The long-term service utilization data were collected from the local governmental office. Frailty was examined by the in-home structured assessment conducted by local health and welfare professionals. As frailty indicators, we measured subjects' frailty using the Kaigo-Yobo-Checklist (CL frailty), handgrip strength, body mass index, depression, and cognitive function. Long-term service utilization patterns were classified into five patterns: (1) home helper service only, (2) day care service only, (3) home helper and day care service, (4) one or more other services (using at least one other service regardless of home helper or day care), and (5) no service utilization. Odds ratios (ORs) of each frailty indicator were estimated by service utilization patterns by using logistic regression analyses adjusted for demographic characteristics, with the other services group as the reference category. Out of 710 subjects (100%), the proportions of the service utilization patterns were as follows: home helper service only, 17.9%; day care service only, 15.6%; home helper and day care service, 13.1%; one or more other services, 27.0%; and no service utilization, 26.3%. The logistic regression analyses showed that compared with the one or more other services group, the day care service only group had lower odds of CL frailty (OR=0.57, 95% confidence interval (CI)=0.34 to 0.95) and lower odds of low handgrip strength (OR=0.59, 95% CI=0.35 to 1.00). The no service utilization group had lower odds of CL frailty (OR=0.50, 95% CI=0.32 to 0.79) and lower odds of low handgrip strength (OR=0.58, 95
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Nordberg, Ann; Dahlgren Sandberg, Annika; Miniscalco, Carmela
2015-01-01
Research on retelling ability and cognition is limited in children with cerebral palsy (CP) and speech impairment. To explore the impact of expressive and receptive language, narrative discourse dimensions (Narrative Assessment Profile measures), auditory and visual memory, theory of mind (ToM) and non-verbal cognition on the retelling ability of children with CP and speech impairment. Fifteen speaking children with speech impairment (seven girls, eight boys) (mean age = 11 years, SD = 1;4 years), and different types of CP and different levels of gross motor and cognitive function participated in the present study. Story retelling skills were tested and analysed with the Bus Story Test (BST) and the Narrative Assessment Profile (NAP). Receptive language ability was tested with the Test for Reception of Grammar-2 (TROG-2) and the Peabody Picture Vocabulary Test - IV (PPVT-IV). Non-verbal cognitive level was tested with the Raven's coloured progressive matrices (RCPM), memory functions assessed with the Corsi block-tapping task (CB) and the Digit Span from the Wechsler Intelligence Scale for Children-III. ToM was assessed with the false belief items of the two story tests "Kiki and the Cat" and "Birthday Puppy". The children had severe problems with retelling ability corresponding to an age-equivalent of 5;2-6;9 years. Receptive and expressive language, visuo-spatial and auditory memory, non-verbal cognitive level and ToM varied widely within and among the children. Both expressive and receptive language correlated significantly with narrative ability in terms of NAP total scores, so did auditory memory. The results suggest that retelling ability in the children with CP in the present study is dependent on language comprehension and production, and memory functions. Consequently, it is important to examine retelling ability together with language and cognitive abilities in these children in order to provide appropriate support. © 2015 Royal College of Speech and
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Shang, Nan; Styles, Suzy J.
2017-01-01
Studies investigating cross-modal correspondences between auditory pitch and visual shapes have shown children and adults consistently match high pitch to pointy shapes and low pitch to curvy shapes, yet no studies have investigated linguistic-uses of pitch. In the present study, we used a bouba/kiki style task to investigate the sound/shape mappings for Tones of Mandarin Chinese, for three groups of participants with different language backgrounds. We recorded the vowels [i] and [u] articulated in each of the four tones of Mandarin Chinese. In Study 1 a single auditory stimulus was presented with two images (one curvy, one spiky). In Study 2 a single image was presented with two auditory stimuli differing only in tone. Participants were asked to select the best match in an online ‘Quiz.’ Across both studies, we replicated the previously observed ‘u-curvy, i-pointy’ sound/shape cross-modal correspondence in all groups. However, Tones were mapped differently by people with different language backgrounds: speakers of Mandarin Chinese classified as Chinese-dominant systematically matched Tone 1 (high, steady) to the curvy shape and Tone 4 (falling) to the pointy shape, while English speakers with no knowledge of Chinese preferred to match Tone 1 (high, steady) to the pointy shape and Tone 3 (low, dipping) to the curvy shape. These effects were observed most clearly in Study 2 where tone-pairs were contrasted explicitly. These findings are in line with the dominant patterns of linguistic pitch perception for speakers of these languages (pitch-change, and pitch height, respectively). Chinese English balanced bilinguals showed a bivalent pattern, swapping between the Chinese pitch-change pattern and the English pitch-height pattern depending on the task. These findings show for that the supposedly universal pattern of mapping linguistic sounds to shape is modulated by the sensory properties of a speaker’s language system, and that people with high functioning
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Ho, Hoi Ki Kiki; Görges, Matthias; Portales-Casamar, Elodie
2018-05-14
ensuring protection of privacy while achieving efficient data access, research institutions will be able to maximize their research capacity, a crucial step towards achieving the ultimate and shared goal between all stakeholders-to better health outcomes. ©Hoi Ki Kiki Ho, Matthias Görges, Elodie Portales-Casamar. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 14.05.2018.