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人类疾病研究的新焦点:中性肽链内切酶(NEP)——NEP生理功能及其潜在调控因子研究之进展(英文)

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中国生物化学与分子生物学报 2007年第2期23卷 85-92页

作者：洪玥 Antony j.turner 英国利兹大学细胞与分子生物学学院

Neprilysin(NEP)是M13锌金属蛋白酶家族的一种Ⅱ型整合细胞膜糖蛋白.自从1974年首次被定义以来,NEP作为一种神经肽的降解酶,已经被发现广泛地存在于中枢神经系统以及外周各种组织中,并具有众多组织特异性功能.其中,NEP具有两大重要生理... 详细信息

Neprilysin(NEP)是M13锌金属蛋白酶家族的一种Ⅱ型整合细胞膜糖蛋白.自从1974年首次被定义以来,NEP作为一种神经肽的降解酶,已经被发现广泛地存在于中枢神经系统以及外周各种组织中,并具有众多组织特异性功能.其中,NEP具有两大重要生理功能:一是NEP通过抑制细胞迁移增殖并诱导细胞程序性死亡具有抗肿瘤作用,这依赖它的酶学特性以及与涉及细胞信号转导通路的关键分子直接的蛋白-蛋白间相互作用;另外,NEP具有神经保护作用,这主要通过阻止神经毒物——淀粉样蛋白Aβ在大脑中的聚集来实现.通过研究各种人类疾病的进展,目前发现这些疾病经常伴随有NEP表达的削弱和活性下降.基于这些发现,调控NEP在病理细胞中的不同水平正在逐渐被认可为具有治疗应用前景的一种策略,从而达到恢复正常的细胞功能并缓解病症的目的.现阶段的研究重点,主要在于揭示涉及NEP的表达以及活性的一些调控机制,并且获得了大量鼓舞人心的研究成果.例如,男性荷尔蒙已知是前列腺中NEP的转录调节因子.除它之外,最新研究结果还发现,女性雌激素,柳栎的水合萃取物,绿茶的一些组分,各种神经肽比如韩蛙皮素和生长激素抑制素以及淀粉样前体蛋白的胞内区,也都对NEP的表达和活性有刺激作用.

关键词：中性肽链内切酶(NEP) 抗肿瘤神经保护 NEP调节

Deep learning based classification of sheep behaviour from accelerometer data with imbalance

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Information Processing in Agriculture 2023年第3期10卷 377-390页

作者： Kirk E.turner Andrew Thompson ian Harris Mark Ferguson Ferdous Sohel Discipline of Information Technology Murdoch UniversityMurdochWA 6150Australia Centre for Crop and Food Innovation Food Futures InstituteMurdoch UniversityMurdochWA 6150Australia College of Science HealthEngineering and EducationMurdoch UniversityMurdochWA 6150Australia neXtgen Agri Saint MartinsChristchurch 8022New Zealand

Classification of sheep behaviour from a sequence of tri-axial accelerometer data has the potential to enhance sheep *** behaviour is inherently imbalanced(e.g.,more ruminating than walking)resulting in underperforming classification for the minority activities which hold *** works have not addressed class imbalance and use traditional machine learning techniques,e.g.,Random Forest(RF).We investigated Deep Learning(DL)models,namely,Long Short Term Memory(LSTM)and Bidirectional LSTM(BLSTM),appropriate for sequential data,from imbalanced *** data sets were collected in normal grazing conditions using jaw-mounted and earmounted *** to this study,alongside typical single classes,e.g.,walking,depending on the behaviours,data samples were labelled with compound classes,e.g.,walking_-*** number of steps a sheep performed in the observed 10 s time window was also recorded and incorporated in the *** designed several multi-class classification studies with imbalance being addressed using synthetic *** models achieved superior performance to traditional ML models,especially with augmented data(e.g.,4-Class+Steps:LSTM 88.0%,RF 82.5%).DL methods showed superior generalisability on unseen sheep(i.e.,F1-score:BLSTM 0.84,LSTM 0.83,RF 0.65).LSTM,BLSTM and RF achieved sub-millisecond average inference time,making them suitable for real-time *** results demonstrate the effectiveness of DL models for sheep behaviour classification in grazing *** results also demonstrate the DL techniques can generalise across different *** study presents a strong foundation of the development of such models for real-time animal monitoring.

关键词： Sheep behaviour classification Data synthesis Class imbalance Grazing sheep

Fluctuating resources,disturbance and plant strategies:diverse mechanisms underlying plant invasions

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journal of Arid Land 2013年第3期5卷 284-297页

作者： ian j RADFORD CSIRO Sustainable Ecosystems Davies LaboratoryPrivate Mailbag POAitkenvale 4814Australia Botany Department University of OtagoPO Box 56Dunedin 9054New Zealand

This paper examines the hypothesis that non-native plant invasions are related to fluctuating resource availability as proposed by Davis et al. （2000）. I measured relative functional responses of both invasive and native plants to changed resource availability due to nutrient enrichment and rainfall, and to increased disturbance. Data are presented from studies in two contrasting ecosystems. First is a series of glasshouse and field experiments on the invader Hieracium lepidulum and associated invasive and native species in subalpine temperate New Zealand. Second is a field study of invasive and native plant responses to altered disturbance regimes and rainfall from tropical savannas of north eastern Australia. Invaders responded differently from native species to changes in resource availability in both subalpine and tropical studies. However, invaders differed among themselves showing that different species exploit different functional niches to invade their respective habitats. These findings contribute to the contention that the fluctuating resource hypothesis does not provide a universal explanation for plant invasions. The diverse functional responses to increased resource availability among invaders in this and previous studies suggest that the cause of invasion depends on unique combinations of habitat and functional attributes of invaders and native assemblages. Such findings imply that universal predictions of what will happen under climate change scenarios across the globe will be difficult to make.

关键词： plant invasion plant strategies C-S-R triangle fluctuating resources disturbance

The Impact of Sleep-Wake Behaviour on Tennis Match Performance in junior State Grade Tennis Players

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journal of Science in Sport and Exercise 2023年第2期5卷 156-166页

作者： Mitchell turner Philipp Beranek ian C.Dunican Travis Cruickshank School of Medical and Health Sciences Edith Cowan University270 Joondalup DrivePerthWA 6027Australia Centre for Sleep Science School of Human SciencesThe University of Western AustraliaPerthWA 6009Australia Centre for Precision Health School of Medical and Health SciencesEdith Cowan UniversityPerthAustralia Perron Institute for Neurological and Translational Sciences PerthAustralia

Purpose To date,no study has investigated the extent to which sleep-wake behaviour(SWB)influences match performance in junior tennis *** study aimed to assess the influence of SWB for the week and night before on match performance,particularly match analytics and *** This study recruited 10 junior state grade tennis players who wore an actigraphy device and completed a sleep diary for the week before their match on two separate occasions throughout their competition *** wore a global positioning system device to track their movement during matches,and an experienced tennis coach recorded players'match *** This study showed that the sleep fragmentation index was significantly lower the week before matches in females who had won than those who had ***,the sleep fragmentation index was significantly lower the night before a given match than the week *** sleep fragmentation index and sleep latency significantly influenced match performance in junior tennis *** percentage of second serves points won differed between match wins and losses for male players,while winners and forced errors differed for female *** These findings provide a detailed profile of tennis match play in junior state grade *** individual differences,reduced restlessness the night before a match coincides with increased match performance.

关键词： Sleep fragmentation Tennis analytics Global positioning system Sleep quality Sleep duration

Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration

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International journal of Ophthalmology(English edition) 2011年第1期4卷 85-88页

作者： ian j Constable ian L McAllister Timothy Isaacs Lions Eye Institute Centre for Ophthalmology and Visual ScienceUniversity of Western AustraliaPerthWestern AustraliaAustralia

AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing jection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.

关键词： age-related macular degeneration anti-VEGF bevacizumab ranibizumab choroidal neovascularization

Continued Fraction Cartesian to Geodetic Coordinate Transformation

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Computer Modeling in Engineering & Sciences 2016年第3期111卷 257-268页

作者： j.D.turner A.Alnaqeb A.Bani Younes Khalifa University Abu DhabiUAE

A singularity-free perturbation solution is presented for inverting the Cartesian to Geodetic *** approaches for inverting the transformation use the natural ellipsoidal coordinates,this work explores the use of the satellite ground-track vector as the differential correction *** geodetic latitude is recovered by well-known elementary means.A high-accuracy highperformance 3D vector-valued continued fraction iteration is *** convergence is achieved because the starting guess for the ground-track vector provides a maximum error of 30 m for the satellite height above the Earth’s surface,throughout the LEO-GEO range of *** a result,a single iteration of the continued fraction iteration yields a maximum error for the satellite height of 10??11 *** maximum error for the geodetic anomaly of 10??9 *** coordinate transformation is completed by non-iteratively recovering the satellite height and the geodetic *** Taylor expansions are introduced and no jacobian sensitivity calculations are *** all practical applications the new algorithm provides a closed-form *** accuracy and algorithmic performance of the proposed approach is compared with other state of the art algorithms.

关键词： Geodetic transformation continued fraction singularity-free

Considerations for exerkine research focusing on the response to exercise training

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journal of Sport and Health Science 2024年第2期13卷 130-132页

作者： ian A.j.Darragh Brendan Egan School of Health and Human Performance Dublin City UniversityGlasnevinDublin D09 V209Ireland Florida Institute for Human and Machine Cognition PensacolaFL 32502USA

García-Hermoso and colleagues1 recently published a systematic literature review and meta-analysis on exercise training-induced changes in exerkine concentrations in type 2diabetes mellitus patients,providing a contemporary view on how exerkines respond to exercise *** review prompted us to highlight 2 additional considerations that should be taken into account when studying the response of exerkines to exercise ***,whether exerkines can exhibit discordant responses to acute exercise compared to exercise training,and secondly,the need to consider the residual effects of the most recent exercise bout.

关键词： acute exercise prompt

Opioid growth factor and the treatment of human pancreatic cancer:A review

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World journal of Gastroenterology 2014年第9期20卷 2218-2223页

作者： ian S Zagon Patricia j McLaughlin Department of Neural and Behavioral Sciences Pennsylvania State University College of Medicine Hershey PA 17033 United States

Opioid growth factor (OGF), chemically termed [Met5]-enkephalin, and its receptor, OGF receptor (OGFr), form a biological axis that tonically regulates cell proliferation by delaying the G1/S interface of the cell cycle under homeostatic conditions or in neoplasia. Modulation of the OGF-OGFr pathway mediates the course of pancreatic cancer, with exogenous OGF or upregulation of OGFr repressing growth of human pancreatic cancer cells in culture and in nude mice. OGF therapy alone or in combination with standard chemotherapies such as gemcitabine and 5-fluorouracil results in enhanced inhibition of DNA synthesis and tumor growth. Molecular manipulation of OGFr confirms that the receptor is specific for OGF’s inhibitory action. Preclinical studies have warranted Phase I and Phase II clinical trials using OGF infusions as a treatment for patients with advanced, unresectable pancreatic cancers. OGF, an endogenous neuropeptide, is a safe, non-toxic, and effective biotherapy that utilizes the OGF-OGFr axis to mediate pancreatic tumor progression.

关键词： Enkephalins DNA synthesis Pancreatic adenocarcinoma Opioids Nude mice Receptor transfection

The N-terminus of COX-1 and its effect on cyclooxygenase-1 catalytic activity

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journal of Genetics and Genomics 2010年第2期37卷 117-123页

作者： Sean Phipps Michael j. turner Daniel L. Simmons Chemistry and Biochemistry Department Brigham Young University

Cyclooxygenases are encoded by COX-1 and COX-2. They share over sixty percent sequence identity in human and are similar to each other in their crystallographic structures. One major difference in the primary structure of these two isozymes is the presence of eight amino acids in the amino-terminal region of COX-1 that are not present in COX-2. The function of this amino acid sequence is unknown. In this study, a human COX-1 mutant （Δ7aa） with this sequence removed was studied in parallel with COX-1. Signal peptide cleavage, N-linked glycosylation, protein expression, distribution and dimerization were not affected by the mutation. The mutant was enzymati-cally active and showed the same sensitivity toward aspirin. The KM for the enzyme remained the same as COX-1. However, the Vmax of the COX-1 mutant decreased by 3.3-fold. We conclude that the COX-1 specific amino-terminal sequence has a subtle but detectable effect on COX-1 catalysis.

关键词： COX-1 COX-2 dimerization glycosylation aspirin KM Vmax