TDCMR: Triplet-Based Deep Cross-Modal Retrieval for geo-multimedia data

Mass multimedia data with geographical information (geo-multimedia) are collected and stored on the Internet due to the wide application of location-based services (LBS). How to find the high-level semantic relationship between geo-multimedia data and construct efficient index is crucial for large-scale geo-multimedia retrieval. To combat this challenge, the paper proposes a deep cross-modal hashing framework for geo-multimedia retrieval, termed as Triplet-based Deep Cross-Modal Retrieval (TDCMR), which utilizes deep neural network and an enhanced triplet constraint to capture high-level semantics. Besides, a novel hybrid index, called TH-Quadtree, is developed by combining cross-modal binary hash codes and quadtree to support high-performance search. Extensive experiments are conducted on three common used benchmarks, and the results show the superior performance of the proposed method

CDK5-dependent BAG3 degradation modulates synaptic protein turnover

阿尔茨海默病（AD）是严重威胁人类健康的重大神经系统疾病，AD的发生发展与衰老密切相关，目前临床治疗方法十分有限。因此迫切需要从AD致病早期入手，发现和鉴定导致AD神经功能紊乱的机制和靶点，为AD的早期防治提供基础。张杰教授及其团队从高通量磷酸化蛋白质组学入手，系统研究了CDK5在神经细胞中的磷酸化底物，鉴定出了在蛋白质量控制中发挥重要功能的BAG3蛋白是CDK5的全新底物。课题组从磷酸化蛋白质组学入手，发现和阐明了细胞周期蛋白激酶5（CDK5）通过调控BAG3在维持突触蛋白水平调控中的作用机制，及其在阿尔茨海默病（AD）发生发展中的机理。 该研究是多个团队历时8年合作完成的，香港中文大学的周熙文教授、美国匹兹堡大学的Karl Herrup教授、美国Sanford-Burnham研究所的许华曦教授、美国梅奥医学中心的卜国军教授，厦门大学医学院的文磊教授、张云武教授、赵颖俊教授、薛茂强教授，军事医学科学院的袁增强教授等都参与了该工作。 厦门大学医学院2012级博士生周杰超等为文章的第一作者，张杰教授为通讯作者。Background Synaptic protein dyshomeostasis and functional loss is an early invariant feature of Alzheimer’s disease (AD), yet the unifying etiological pathway remains largely unknown. Knowing that cyclin-dependent kinase 5 (CDK5) plays critical roles in synaptic formation and degeneration, its phosphorylation targets were re-examined in search for candidates with direct global impacts on synaptic protein dynamics, and the associated regulatory network was also analyzed. Methods Quantitative phospho-proteomics and bioinformatics analyses were performed to identify top-ranked candidates. A series of biochemical assays were used to investigate the associated regulatory signaling networks. Histological, electrochemical and behavioral assays were performed in conditional knockout, shRNA-mediated knockdown and AD-related mice models to evaluate its relevance to synaptic homeostasis and functions. Results Among candidates with known implications in synaptic modulations, BCL2-associated athanogene-3 (BAG3) ranked the highest. CDK5-mediated phosphorylation on Ser297/Ser291 (Mouse/Human) destabilized BAG3. Loss of BAG3 unleashed the selective protein degradative function of the HSP70 machinery. In neurons, this resulted in enhanced degradation of a number of glutamatergic synaptic proteins. Conditional neuronal knockout of Bag3 in vivo led to impairment of learning and memory functions. In human AD and related-mouse models, aberrant CDK5-mediated loss of BAG3 yielded similar effects on synaptic homeostasis. Detrimental effects of BAG3 loss on learning and memory functions were confirmed in these mice, and such were reversed by ectopic BAG3 re-expression. Conclusions Our results highlight that neuronal CDK5-BAG3-HSP70 signaling axis plays a critical role in modulating synaptic homeostasis. Dysregulation of the signaling pathway directly contributes to synaptic dysfunction and AD pathogenesis.This work was supported by the National Science Foundation in China (Grant: 31571055, 81522016, 81271421 to J.Z.; 81801337 to L.L; 81774377 and 81373999 to L.W.); Fundamental Research Funds for the Central Universities of China-Xiamen University (Grant: 20720150062, 20720180049 and 20720160075 to J.Z.); Fundamental Research Funds for Fujian Province University Leading Talents (Grant JAT170003 to L.L); Hong Kong Research Grants Council (HKUST12/CRF/13G, GRF660813, GRF16101315, AoE/M-05/12 to K.H.; GRF16103317, GRF16100718 and GRF16100219 to H.-M,C.); Offices of Provost, VPRG and Dean of Science, HKUST (VPRGO12SC02 to K.H.); Chinese University of Hong Kong (CUHK) Improvement on Competitiveness in Hiring New Faculty Funding Scheme (Ref. 133), CUHK Faculty Startup Fund and Alzheimer’s Association Research Fellowship (AARF-17-531566) to H.-M, C. 该研究受到了国家自然科学基金、厦门大学校长基金、福建省卫生教育联合攻关基金等的资助