bluuebunny/crossref_metadata_2025_split huggingface dataset:
The peroxisome proliferator‐activated receptors in cardiovascular diseases: experimental benefits and clinical challenges
Authors: Cheang Wai San , Tian Xiao Yu , Wong Wing Tak , Huang Yu 
Published: December 2014

The peroxisome proliferator‐activated receptors, PPARα, PPARβ/δ and PPARγ, are ligand‐activated transcriptional factors belonging to the nuclear receptors superfamily and they are known to play important roles in glucose and lipid metabolism. Experimental studies in animal models of metabolic diseases have also revealed that activation of PPARs protects against the vascular complications of diabetes, hypertension, atherosclerosis, myocardial infarction and stroke, through exerting their anti‐inflammatory, anti‐atherogenic and antioxidant effects. In clinical trials and post‐market surveillance, agonists of PPARs have been shown to effectively prevent cardiovascular events. However, adverse effects, particularly for PPARγ agonists, are also observed with the use of investigational PPAR agonists and even some approved drugs. Further exploration of underlying mechanisms is needed to develop novel ways of PPAR activation without causing serious side effects. This article reviews the cardiovascular effects of PPARs, with emphasis on the therapeutic potential of PPAR agonists in combating metabolic vascular diseases.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in
this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
S1P‐induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo: molecular and cellular mechanisms
Authors: Roviezzo F , Sorrentino R , Bertolino A , De Gruttola L , Terlizzi M , Pinto A , Napolitano M , Castello G , D'Agostino B , Ianaro A , Sorrentino R , Cirino G 
Published: December 2014

Background and PurposeSphingosine‐1‐phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung.Experimental ApproachBALB/c, mast cell‐deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed.Key ResultsS1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2, IgE, IL‐4 and IL‐13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell‐deficient Kit W‐sh/W‐sh mice injected with S1P did not display airway smooth muscle hyper‐reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti‐CD23 antibody B3B4, which blocks IgE production, inhibited both S1P‐induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper‐reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T‐cells harvested from S1P‐treated mice presented all the features elicited by S1P in the lung.Conclusions and ImplicationsS1P triggers a cascade of events that sequentially involves T‐cells, IgE and mast cells reproducing several asthma‐like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently‐used drugs as well as in the development of new therapeutic approaches for asthma‐like diseases.
AT‐1001: a high‐affinity α3β4 nAChR ligand with novel nicotine‐suppressive pharmacology
Authors: Cippitelli Andrea , Wu Jinhua , Gaiolini Kelly A , Mercatelli Daniela , Schoch Jennifer , Gorman Michelle , Ramirez Alejandra , Ciccocioppo Roberto , Khroyan Taline V , Yasuda Dennis , Zaveri Nurulain T , Pascual Conrado , Xie Xinmin (Simon) , Toll Lawrence 
Published: December 2014

Background and PurposeThe α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT‐1001 has been recently described as a high‐affinity and selective α3β4 nAChR antagonist that blocks nicotine self‐administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine‐suppressive effects of AT‐1001.Experimental ApproachEffects of AT‐1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.Key ResultsAT‐1001 and its analogue AT‐1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT‐1001 and varenicline also had very different in vivo properties. Firstly, AT‐1001 did not exhibit reinforcing properties per se while varenicline was self‐administered. Secondly, systemic treatment with AT‐1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT‐1001 selectively blocked nicotine self‐administration without altering alcohol lever pressing as assessed in an operant co‐administration paradigm.Conclusions and ImplicationsThese findings describe a more complex AT‐1001 in vitro profile than previously appreciated and provide further support for the potential of AT‐1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications.
Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer
Authors: Ema Akira , Yamashita Keishi , Ushiku Hideki , Kojo Ken , Minatani Naoko , Kikuchi Mariko , Mieno Hiroaki , Moriya Hiromitsu , Hosoda Kei , Katada Natsuya , Kikuchi Shiro , Watanabe Masahiko 
Published: December 2014

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S‐1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S‐1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF‐1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5‐year Relapse Free Survival (5y‐RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF‐1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF‐1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11–2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3‐positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.
Determinants of participation in prostate cancer screening: A simple analytical framework to account for healthy‐user bias
Authors: Tabuchi Takahiro , Nakayama Tomio , Fukushima Wakaba , Matsunaga Ichiro , Ohfuji Satoko , Kondo Kyoko , Kawano Eiji , Fukuhara Hiroyuki , Ito Yuri , Oshima Akira 
Published: December 2014

In Japan at present, fecal occult blood testing (FOBT) is recommended for cancer screening while routine population‐based prostate‐specific antigen (PSA) screening is not. In future it may be necessary to increase participation in the former and decrease it in the latter. Our objectives were to explore determinants of PSA‐screening participation while simultaneously taking into account factors associated with FOBT. Data were gathered from a cross‐sectional study conducted with random sampling of 6191 adults in Osaka city in 2011. Of 3244 subjects (return rate 52.4%), 936 men aged 40–64 years were analyzed using log‐binomial regression to explore factors related to PSA‐screening participation within 1 year. Only responders for cancer screening, defined as men who participated in either FOBT or PSA‐testing, were used as main study subjects. Men who were older (prevalence ratio [PR] [95% confidence interval (CI)] = 2.17 [1.43, 3.28] for 60–64 years compared with 40–49 years), had technical or junior college education (PR [95% CI] = 1.76 [1.19, 2.59] compared with men with high school or less) and followed doctors' recommendations (PR [95% CI] = 1.50 [1.00, 2.26]) were significantly more likely to have PSA‐screening after multiple variable adjustment among cancer‐screening responders. Attenuation in PR of hypothesized common factors was observed among cancer‐screening responders compared with the usual approach (among total subjects). Using the analytical framework to account for healthy‐user bias, we found three factors related to participation in PSA‐screening with attenuated association of common factors. This approach may provide a more sophisticated interpretation of participation in various screenings with different levels of recommendation.
The Identity‐Location Binding Problem
Authors: Howe Piers D. L. , Ferguson Adam 
Published: December 2014

AbstractThe binding problem is fundamental to visual perception. It is the problem of associating an object's visual properties with itself and not with some other object. The problem is made particular difficult because different properties of an object, such as its color, shape, size, and motion, are often processed independently, sometimes in different cortical areas. The results of these separate analyses have to be combined before the object can be seen as a single coherent entity as opposed to a collection of unconnected features. Visual bindings are typically initiated and updated in a serial fashion, one object at a time. Here, we show that one type of binding, location‐identity bindings, can be updated in parallel. We do this by using two complementary techniques, the simultaneous‐sequential paradigm and systems factorial technology. These techniques make different assumptions and rely on different behavioral measures, yet both came to the same conclusion.
MOR1 Expression in Gastric Cancer: A Biomarker Associated With Poor Outcome
Authors: Yao Ya‐sai , Yao Ru‐yong , Zhuang Li‐kun , Qi Wei‐wei , Lv Jing , Zhou Fei , Qiu Wen‐sheng , Yue Lu 
Published: December 2014

AbstractBackgroundAt present, the expression of MOR1 and its function in gastric cancer remains unclear with evidence suggesting that it is to be involved in tumor progression and metastasis. The study was to assess the clinicopathologic relevance and prognostic value of MOR1 expression in gastric cancer.MethodsReal‐time quantitative RT‐PCR and immunohistochemical staining were used to detect MOR1 expression in primary gastric cancerous surgical specimens and adjacent nontumorous tissues.ResultsHigh MOR1 expression was detected in cancerous tumor compared with their adjacent nontumorous tissues. In addition, the chi‐square test revealed that high MOR1 expression was significantly correlated with depth of invasion (p = 0.006), lymph node metastasis (p = 0.001), distant metastasis (p = 0.017), and TNM staging (p = 0.027). Moreover, Kaplan–Meier analysis revealed a significant association between MOR1 expression and overall survival. High expression of MOR1 was identified as an independent and significant predictor gene of reduced postoperative survival.ConclusionWe conclude that MOR1 expression may be a useful biomarker for better prediction of the clinical outcome and management of gastric cancer patients.
TheNativeAmerican Organic Garden: Using Service Learning as a Site of Resistance
Authors: Chollett Donna L. 
Published: December 2014

AbstractAs educators, we owe it to our students to enable them to transgress structural impediments and to create sustainable alternatives from the margins of the industrial agro‐food system. Policies of assimilation, allotment, and enclosure of theNativeAmerican commons and ecosystems brought devastation toNative cultures. Dependence on government commodities replacedNative food sovereignty and contributed to malnutrition, obesity, and diabetes as diets responded to corporately produced and processed foods. Young people often feel disempowered and ask how they might confront such formidable forces as corporate control of our agro‐food system, destruction of natural resources, and threats to human health. Service learning at a formerNativeAmerican boarding school, now a university campus, empowered students to create a community of learning and practice that resulted in aNativeAmericanOrganicGarden. Based onNative values, the garden serves the community's needs for healthy, locally produced food.
Organic Designs and Agrarian Practice in Uttarakhand, India
Authors: Galvin Shaila Seshia 
Published: December 2014

AbstractThis article brings together ethnographic fieldwork with archival research to show that debates about human agency are central to the contemporary meaning of organic agriculture in the northern Indian state of Uttarakhand. Through a study of an initiative taken by the Uttarakhand state government to promote certified organic agriculture among the region's smallholder farmers, the article demonstrates that debates about human agency in relation to soil, manure, and compost are bound up with historical as well as ongoing processes of state formation in the Uttarakhand region. After examining how state officials recognize certain forms of agricultural practice as agentive, but not others, the article concludes with an exploration of how farmers navigate newfound agrarian identities.
Ensemble perception of size in 4–5‐year‐old children
Authors: Sweeny Timothy D. , Wurnitsch Nicole , Gopnik Alison , Whitney David 
Published: November 2014

AbstractGroups of objects are nearly everywhere we look. Adults can perceive and understand the ‘gist’ of multiple objects at once, engaging ensemble‐coding mechanisms that summarize a group's overall appearance. Are these group‐perception mechanisms in place early in childhood? Here, we provide the first evidence that 4–5‐year‐old children use ensemble coding to perceive the average size of a group of objects. Children viewed a pair of trees, with each containing a group of differently sized oranges. We found that, in order to determine which tree had the larger oranges overall, children integrated the sizes of multiple oranges into ensemble representations. This pooling occurred rapidly, and it occurred despite conflicting information from numerosity, continuous extent, density, and contrast. An ideal observer analysis showed that although children's integration mechanisms are sensitive, they are not yet as efficient as adults’. Overall, our results provide a new insight into the way children see and understand the environment, and they illustrate the fundamental nature of ensemble coding in visual perception.
The brain adapts to orthography with experience: evidence from English and Chinese
Authors: Cao Fan , Brennan Christine , Booth James R. 
Published: November 2014

AbstractUsing functional magnetic resonance imaging (fMRI), we examined the process of language specialization in the brain by comparing developmental changes in two contrastive orthographies: Chinese and English. In a visual word rhyming judgment task, we found a significant interaction between age and language in left inferior parietal lobule and left superior temporal gyrus, which was due to greater developmental increases in English than in Chinese. Moreover, we found that higher skill only in English children was correlated with greater activation in left inferior parietal lobule. These findings suggest that the regions associated with phonological processing are essential in English reading development. We also found greater developmental increases in English than in Chinese in left inferior temporal gyrus, suggesting refinement of this region for fine‐grained word form recognition. In contrast, greater developmental increases in Chinese than in English were found in right middle occipital gyrus, suggesting the importance of holistic visual‐orthographic analysis in Chinese reading acquisition. Our results suggest that the brain adapts to the special features of the orthography by engaging relevant brain regions to a greater degree over development.
The late positive potential predicts emotion regulation strategy use in school‐aged children concurrently and two years later
Authors: Babkirk Sarah , Rios Victor , Dennis Tracy A. 
Published: November 2014

AbstractThe ability to use cognitive emotion regulation strategies such as reappraisal may be a core component of emotional competence across development, but due to methodological challenges in measuring such strategies, they are rarely studied in young children. One neurophysiological measure, the late positive potential (LPP), has been examined in response to reappraisal as a potential neurosignature for emotion regulatory capacity in adults. The association between the LPP and emotion regulatory capacity in children is unknown. The present study examined whether the LPP during reappraisal could predict greater observed adaptive emotion regulation strategy use in school‐aged children over a two‐year period. Thirty‐two 5‐ to 7‐year‐olds participated in two identical lab visits spaced two years apart. EEG was continuously recorded during a computerized reappraisal task in which children viewed unpleasant images paired with either reappraisal or negative stories. Next they completed a disappointing and a frustrating task during which emotion regulation strategies were observed. As predicted, children who showed reappraisal‐induced reductions in the LPP at the first assessment used significantly more adaptive ER strategies concurrently and two years later. These findings provide observation‐based evidence that the LPP may be a viable neurosignature for emotion regulatory capacity in children.
Concurrent and lasting effects of emotion regulation on amygdala response in adolescence and young adulthood
Authors: Silvers Jennifer A. , Shu Jocelyn , Hubbard Alexa D. , Weber Jochen , Ochsner Kevin N. 
Published: November 2014

AbstractThis study used functional MRI (fMRI) to examine a novel aspect of emotion regulation in adolescent development: whether age predicts differences in both the concurrent and lasting effects of emotion regulation on amygdala response. In the first,active regulation, phase of the testing session,fMRIdata were collected while 56 healthy individuals (age range: 10.50–22.92 years) reappraised aversive stimuli so as to diminish negative responses to them. After a short delay, the second,re‐presentation, phase involved passively viewing the aversive images from the reappraisal task. During active regulation, older individuals showed greater drops in negative affect and inverse rostrolateral prefrontal‐amygdala connectivity. During re‐presentation, older individuals continued to show lasting reductions in the amygdala response to aversive stimuli they had previously reappraised, an effect mediated by rostrolateral PFC. These data suggest that one source of heightened emotionality in adolescence is a diminished ability to cognitively down‐regulate aversive reactions.
Processing of audiovisually congruent and incongruent speech in school‐age children with a history of specific language impairment: a behavioral and event‐related potentials study
Authors: Kaganovich Natalya , Schumaker Jennifer , Macias Danielle , Gustafson Dana 
Published: November 2014

AbstractPrevious studies indicate that at least some aspects of audiovisual speech perception are impaired in children with specific language impairment (SLI). However, whether audiovisual processing difficulties are also present in older children with a history of this disorder is unknown. By combining electrophysiological and behavioral measures, we examined perception of both audiovisually congruent and audiovisually incongruent speech in school‐age children with a history of SLI (H‐SLI), their typically developing (TD) peers, and adults. In the first experiment, all participants watched videos of a talker articulating syllables ‘ba’, ‘da’, and ‘ga’ under three conditions – audiovisual (AV), auditory only (A), and visual only (V). The amplitude of the N1 (but not of the P2) event‐related component elicited in the AV condition was significantly reduced compared to the N1 amplitude measured from the sum of the A and V conditions in all groups of participants. Because N1 attenuation to AV speech is thought to index the degree to which facial movements predict the onset of the auditory signal, our findings suggest that this aspect of audiovisual speech perception is mature by mid‐childhood and is normal in the H‐SLI children. In the second experiment, participants watched videos of audivisually incongruent syllables created to elicit the so‐called McGurk illusion (with an auditory ‘pa’ dubbed onto a visual articulation of ‘ka’, and the expectant perception being that of ‘ta’ if audiovisual integration took place). As a group, H‐SLI children were significantly more likely than either TD children or adults to hear the McGurk syllable as ‘pa’ (in agreement with its auditory component) than as ‘ka’ (in agreement with its visual component), suggesting that susceptibility to the McGurk illusion is reduced in at least some children with a history of SLI. Taken together, the results of the two experiments argue against global audiovisual integration impairment in children with a history of SLI and suggest that, when present, audiovisual integration difficulties in this population likely stem from a later (non‐sensory) stage of processing.
Core geometry in perspective
Authors: Dillon Moira R. , Spelke Elizabeth S. 
Published: November 2014

AbstractResearch on animals, infants, children, and adults provides evidence that distinct cognitive systems underlie navigation and object recognition. Here we examine whether and how these systems interact when children interpret 2D edge‐based perspectival line drawings of scenes and objects. Such drawings serve as symbols early in development, and they preserve scene and object geometry from canonical points of view. Young children show limits when using geometry both in non‐symbolic tasks and in symbolic map tasks that present 3D contexts from unusual, unfamiliar points of view. When presented with the familiar viewpoints in perspectival line drawings, however, do children engage more integrated geometric representations? In three experiments, children successfully interpreted line drawings with respect to their depicted scene or object. Nevertheless, children recruited distinct processes when navigating based on the information in these drawings, and these processes depended on the context in which the drawings were presented. These results suggest that children are flexible but limited in using geometric information to form integrated representations of scenes and objects, even when interpreting spatial symbols that are highly familiar and faithful renditions of the visual world.