Dopamine D-3 receptors regulate GABA(A) receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens

The dopamine D-3 receptor, which is highly enriched in nucleus accumbens (NAc), has been suggested to play an important role in reinforcement and reward. To understand the potential cellular mechanism underlying D-3 receptor functions, we examined the effect of D-3 receptor activation on GABA(A) receptor (GABA(A)R)-mediated current and inhibitory synaptic transmission in medium spiny neurons of NAc. Application of PD128907 [(4aR, 10bR)-3,4a, 4,10b-tetrahydro-4-propyl-2H, 5H-[1] benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], a specific D-3 receptor agonist, caused a significant reduction of GABAAR current in acutely dissociated NAc neurons and miniature IPSC amplitude in NAc slices. This effect was blocked by dialysis with a dynamin inhibitory peptide, which prevents the clathrin/activator protein 2 (AP2)-mediated GABA(A) receptor endocytosis. In addition, the D-3 effect on GABA(A)R current was prevented by agents that manipulate protein kinase A (PKA) activity. Infusion of a peptide derived from GABA(A) beta subunits, which contains an atypical binding motif for the clathrin AP2 adaptor complex and the major PKA phosphorylation sites and binds with high affinity to AP2 only when dephosphorylated, diminished the D-3 regulation of IPSC amplitude. The phosphorylated equivalent of the peptide was without effect. Moreover, PD128907 increased GABAAR internalization and reduced the surface expression of GABA(A) receptor beta subunits in NAc slices, which was prevented by dynamin inhibitory peptide or cAMP treatment. Together, our results suggest that D-3 receptor activation suppresses the efficacy of inhibitory synaptic transmission in NAc by increasing the phospho-dependent endocytosis of GABA(A) receptors

Cascade Residual Learning: A Two-stage Convolutional Neural Network for Stereo Matching

Leveraging on the recent developments in convolutional neural networks (CNNs), matching dense correspondence from a stereo pair has been cast as a learning problem, with performance exceeding traditional approaches. However, it remains challenging to generate high-quality disparities for the inherently ill-posed regions. To tackle this problem, we propose a novel cascade CNN architecture composing of two stages. The first stage advances the recently proposed DispNet by equipping it with extra up-convolution modules, leading to disparity images with more details. The second stage explicitly rectifies the disparity initialized by the first stage; it couples with the first-stage and generates residual signals across multiple scales. The summation of the outputs from the two stages gives the final disparity. As opposed to directly learning the disparity at the second stage, we show that residual learning provides more effective refinement. Moreover, it also benefits the training of the overall cascade network. Experimentation shows that our cascade residual learning scheme provides state-of-the-art performance for matching stereo correspondence. By the time of the submission of this paper, our method ranks first in the KITTI 2015 stereo benchmark, surpassing the prior works by a noteworthy margin.Comment: Accepted at ICCVW 2017. The first two authors contributed equally to this pape

Relative clauses in English-Mandarin bilingual children: Language transfer and development in Singapore

The role of cross-linguistic influence in bilingual children’s development remains a matter of debate. Some researchers have proposed that simultaneously bilingual learners develop the linguistic systems of two languages in the same way as matched monolingual children do. Other researchers have argued that bilingual children show different developmental pathways. This study investigates cross-linguistic influence in the acquisition of relative clauses by English-Mandarin bilingual children in Singapore. The elicitation task included narration and interview tasks. Thirty-six primary school students aged from 6 to 11 years old completed the task in both English and Mandarin. The results reveal that the number of relative clauses increased with age in both languages. Participants had a preference for subject relatives over object relatives. The most frequent error type in Mandarin involves postnominal relative clauses, which have not been reported in monolingual children in the literature and thus can be treated as evidence of transfer from English. The findings of this study provide evidence for cross-linguistic influence in bilingual children's speech.postprin

Hybrid heterogeneous transfer learning through deep learning

Copyright © 2014, Association for the Advancement of Artificial Intelligence. Most previous heterogeneous transfer learning methods learn a cross-domain feature mapping between heterogeneous feature spaces based on a few cross-domain instance-correspondences, and these corresponding instances are assumed to be representative in the source and target domains respectively. However, in many realworld scenarios, this assumption may not hold. As a result, the constructed feature mapping may not be precise due to the bias issue of the correspondences in the target or (and) source domain(s). In this case, a classifier trained on the labeled transformed-sourcedomain data may not be useful for the target domain. In this paper, we present a new transfer learning framework called Hybrid Heterogeneous Transfer Learning (HHTL), which allows the corresponding instances across domains to be biased in either the source or target domain. Specifically, we propose a deep learning approach to learn a feature mapping between crossdomain heterogeneous features as well as a better feature representation for mapped data to reduce the bias issue caused by the cross-domain correspondences. Extensive experiments on several multilingual sentiment classification tasks verify the effectiveness of our proposed approach compared with some baseline methods

The Importance of Serine Phosphorylation of Ameloblastin on Enamel Formation

FAM20C is a newly identified kinase on the secretory pathway responsible for the phosphorylation of serine residues in the Ser-x-Glu/pSer motifs in several enamel matrix proteins. Fam20C-knockout mice showed severe enamel defects very similar to those in the ameloblastin (Ambn)–knockout mice, implying that phosphoserines may have a critical role in AMBN function. To test this hypothesis, we generated amelogenin (Amel) promoter-driven Ambn-transgenic mice, in which Ser⁴⁸, Ser²²⁶, and Ser²²⁷ were replaced by aspartic acid (designated as D-Tg) or alanines (designated as A-Tg). The negative charge of aspartic acid is believed to be able to mimic the phosphorylation state of serine, while alanine is a commonly used residue to substitute serine due to their similar structure. Using Western immunoblotting and quantitative polymerase chain reaction, the authors identified transgenic lines expressing transgenes somewhat higher (Tg+) or much higher (Tg++) than endogenous Ambn. The lower incisors collected from 7-d-old and 7-wk-old mice were analyzed by histology, scanning electron microscopy, immunohistochemistry, and Western immunoblotting to examine the morphology and microstructure changes in enamel, as well as the expression pattern of enamel matrix proteins. The A-Tg+ and A-Tg++ mice displayed severe enamel defects in spite of the expression level of transgenes, while the D-Tg+ and D-Tg++ mice showed minor to mild enamel defects, indicating that the D-Tg transgenes disturbed enamel formation less than the A-Tg transgenes did. Our results suggest that the phosphorylation state of serines is likely an essential component for the integrity of AMBN function

High-efficiency orange and yellow organic light-emitting devices using platinum(II) complexes containing extended π -conjugated cyclometalated ligands as dopant materials

Two luminescent platinum(II) complexes 1 and 2 containing extended π -conjugated cyclometalated ligands have been used as dopant materials for the construction of two high-efficiency organic light-emitting devices I and II. Device I (containing dopant 1) emits orange emission and exhibits a maximum external quantum efficiency of 12.4%, a maximum luminous efficiency of 32.3 cdA, and a maximum power efficiency of 11.2 lmW. Device II (containing dopant 2) emits yellow light and exhibits a maximum external quantum efficiency of 16.1%, a maximum luminous efficiency of 51.8 cdA, and a maximum power efficiency of 23.2 lmW. © 2007 American Institute of Physics.published_or_final_versio

Proliferating tricholemmal tumour: clinicopathological aspects of a case.

We report the case of a 49-year-old man who presented with an enlarging mass over his occipital scalp. The clinical impression was either a squamous cell carcinoma or an unusual adnexal tumour. A wide excision was performed with skin grafting. Gross examination revealed a large exophytic tumour mass measuring 10 cm. Histopathological examination showed a circumscribed, well-differentiated squamoproliferative lesion with a lobulated architecture. Clear cell features, pilar-type keratinisation, microcalcifications and the presence of mucinous degeneration were noted. A diagnosis of proliferating tricholemmal tumour was made. This entity incorporates a spectrum of lesions, ranging from the mostly benign proliferating tricholemmal cyst to tumours having more atypical cellular and invasive features, the latter features correlating with an increased capacity for aggressive behaviour. Management-wise, such tumours require complete excision with follow-up. As the tumours are often large in size at presentation, reconstruction is required

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Less Invasive Phenotype Found in Isocitrate Dehydrogenase-mutated Glioblastomas than in Isocitrate Dehydrogenase Wild-Type Glioblastomas: A Diffusion-Tensor Imaging Study

PURPOSE: To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. MATERIALS AND METHODS: Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study. Patients underwent surgical resection, and tumor samples underwent immunohistochemistry for IDH-1 R132H mutations. DT imaging data were coregistered to the anatomic magnetic resonance study and reconstructed to provide the anisotropic and isotropic components of the DT. The invasive phenotype was determined by using previously published criteria and correlated with IDH-1 mutation status by using the Freeman-Halton extension of the Fisher exact probability test. RESULTS: Nine patients had an IDH-1 mutation and 61 had IDH-1 wild type. All of the patients with IDH-1 mutation had a minimally invasive DT imaging phenotype. Among the IDH-1 wild-type tumors, 42 of 61 (69%) were diffusively invasive glioblastomas, 14 of 61 (23%) were locally invasive, and five of 61 (8%) were minimally invasive (P < .001). CONCLUSION: IDH-mutated glioblastomas have a less invasive phenotype compared with IDH wild type. This finding may have implications for individualizing the extent of surgical resection and radiation therapy volumes.NIHR Clinician Scientist Fellowship (NIHR/CS/009/011); Chang Gung Medical Foundation; Chang Gung Memorial Hospital; Commonwealth Scholarship Commission; Cambridge Commonwealth Overseas Trust; NIHR Cambridge Biomedical Research Centr