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The Epigenome as a therapeutic target for Parkinson's disease

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Neural Regeneration Research 2016年第11期11卷 1735-1738页

作者： shane v.hegarty Aideen M.Sullivan Gerard W.O'Keeffe Department of Anatomy and Neuroscience Biosciences InstituteUniversity College Cork

Parkinson＇s disease （PD） is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This ar- ticle first discusses the present evidence implicating global, and dopaminergic neuron-specific, akerations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase （HAT） and histone deacetylase （HDAC） enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.

关键词： Parkinson＇s disease epigenetics methylation acetylation histone acetyltransferase histonedeacetyIase small molecules

Neurotrophic factors: from neurodevelopmental regulators to novel therapies for Parkinson's disease

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Neural Regeneration Research 2014年第19期9卷 1708-1711页

作者： shane v.hegarty Gerard W.O’Keeffe Aideen M.Sullivan Department of Anatomy and Neuroscience Biosciences InstituteUniversity College Cork

Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther- apies for the incurable and widespread Parkinson＇s disease. In Parkinson＇s disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neurotrophic factors play important regulatory roles in the development, survival and maintenance of specific neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinsoffs disease. Several neurotrophic fac- tors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors： glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.

关键词： Parkinson＇s disease neuroprotection neurotrophic factors nervous system development nigrostriatal dopaminergic neurons glial cell line-derived neurotrophic factor, neurturin, growth/differentiation factor 5

Targeting transcriptional regulators to regenerate midbrain dopaminergic axons in Parkinson's disease

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Neural Regeneration Research 2017年第11期12卷 1814-1815页

作者： shane v.hegarty Aideen M.Sullivan Gerard W.O'Keeffe Department of Anatomy and Neuroscience Western Gateway BuildingUniversity College CorkCorkIreland

Introduction： Parkinson＇s disease （PD） is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostriatal dopaminergic （DA） neurons. This leads to disabling motor symptoms, due to the striatal DA denervation. Despite decades of research, there is still no therapy that can slow, stop or regenerate the dying midbrain DA neurons in PD.

关键词： Targeting transcriptional regulators regenerate midbrain dopaminergic axons

Endohepatology:Arrival at the frontier of interventional endosonography

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World Journal of Gastroenterology 2024年第18期30卷 2397-2401页

作者： shane P Selvanderan Eric Lam Neal Shahidi Department of Medicine University of British ColumbiaVancouver V6Z 1Y6BCCanada

Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound(EUS)are used for the diagnosis and management of liver disease and its sequelae.In this editorial we comment on the article by Gadour et al.The spectrum of EUS-guided procedures includes liver parenchymal and lesional biopsy,abscess drainage,treatment of focal liver lesions,diagnosis of portal hypertension and management of gastric varices.The data suggest that the application of EUS to hepatology is technically feasible and safe,heralding the arrival at a new frontier for EUS.More data,specifically randomised trials comparing EUS to interventional radiology techniques,and continued partnership between endoscopy and hepatology are required to see this field establish itself outside expert tertiary centres.

关键词： Cancer Cirrhosis Endoscopy Endoscopic ultrasound Liver disease

Potential of a fucoidan-rich Ascophyllum nodosum extract to reduce Salmonella shedding and improve gastrointestinal health in weaned pigs naturally infected with Salmonella

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Journal of Animal Science and Biotechnology 2022年第4期13卷 1193-1208页

作者： Brigkita venardou John vO’Doherty shane Maher Marion TRyan vivian Gath Rajeev Ravindran Claire Kiely Gaurav Rajauria Marco Garcia-vaquero Torres Sweeney School of veterinary Medicine University College DublinBelfield Dublin 4Ireland School of Agriculture and Food Science University College DublinBelfield Dublin 4Ireland.

Background:Dietary supplementation with a fucoidan-rich Ascophyllum nodosum extract(ANE),possessing an in vitro anti-Salmonella Typhimurium activity could be a promising on-farm strategy to control Salmonella infection in pigs.The objectives of this study were to:1)evaluate the anti-S.Typhimurium activity of ANE(containing 46.6%fucoidan,18.6%laminarin,10.7%mannitol,4.6%alginate)in vitro,and;2)compare the effects of dietary supplementation with ANE and Zinc oxide(ZnO)on growth performance,Salmonella shedding and selected gut parameters in naturally infected pigs.This was established post-weaning(newly weaned pig experiment)and following regrouping of post-weaned pigs and experimental re-infection with S.Typhimurium(challenge experiment).Results:In the in vitro assay,increasing ANE concentrations led to a linear reduction in S.Typhimurium counts(Pvious experiment that remained on their original dietary treatments(control and high ANE groups with the latter being renamed to ANE group)apart from the ZnO group which transitioned onto a control diet on d 21(ZnO-residual group).These dietary treatments had no effect on performance,faecal scores,Salmonella shedding or colonic and caecal Salmonella counts(P>0.05).ANE supplementation decreased the Enterobacteriaceae counts compared to the control.Enterobacteriaceae counts were also reduced in the ZnO-residual group compared to the control(P<0.05).ANE supplementation decreased the expression of interleukin 22 and transforming growth factor beta 1 in the ileum compared to the control(P<0.05).Conclusions:ANE supplementation was associated with some beneficial changes in the composition of the colonic microbiota,Salmonella shedding,and the expression of inflammatory genes

关键词： Ascophyllum nodosum Gastrointestinal microbiota Inflammation Pig Salmonella Seaweed extract Zinc oxide

MEMS-actuated metasurface Alvarez lens

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Microsystems & Nanoengineering 2020年第1期6卷 334-344页

作者： Zheyi Han shane Colburn Arka Majumdar Karl F.Bohringer Department of Electrical and Computer Engineering University of WashingtonSeattleWashington 98195USA Institute for Nano-Engineered Systems University of WashingtonSeattleWashington 98195USA Department of Physics University of WashingtonSeattleWashington 98195USA Department of Bioengineering University of WashingtonSeattleWashington 98195USA

Miniature lenses with a tunable focus are essential components for many modern applications involving compact optical systems.While several tunable lenses have been reported with various tuning mechanisms,they often face challenges with respect to power consumption,tuning speed,fabrication cost,or production scalability.In this work,we have adapted the mechanism of an Alvarez lens–a varifocal composite lens in which lateral shifts of two optical elements with cubic phase surfaces give rise to a change in the optical power–to construct a miniature,microelectromechanical system(MEMS)-actuated metasurface Alvarez lens.Implementation based on an electrostatic MEMS generates fast and controllable actuation with low power consumption.The utilization of metasurfaces–ultrathin and subwavelength-patterned diffractive optics–as optical elements greatly reduces the device volume compared to systems using conventional freeform lenses.The entire MEMS Alvarez metalens is fully compatible with modern semiconductor fabrication technologies,granting it the potential to be mass-produced at a low unit cost.In the reported prototype operating at 1550 nm wavelength,a total uniaxial displacement of 6.3µm was achieved in the Alvarez metalens with a direct-current(DC)voltage application up to 20v,which modulated the focal position within a total tuning range of 68µm,producing more than an order of magnitude change in the focal length and a 1460-diopter change in the optical power.The MEMS Alvarez metalens has a robust design that can potentially generate a much larger tuning range without substantially increasing the device volume or energy consumption,making it desirable for a wide range of imaging and display applications.

关键词： electrostatic optics adapted

Large-scale synthesis of N-doped carbon capsules supporting atomically dispersed iron for efficient oxygen reduction reaction electrocatalysis

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eScience 2022年第2期2卷 227-234页

作者： Hui Yang Yanfang Liu Xiaolu Liu Xiangke Wang He Tian Geoffrey I.N.Waterhouse Paul E.Krugere shane GTelfer Shengqian Ma Department of Chemistry University of North TexasDentonTX76201United States College of Environmental Science and Engineering North China Electric Power UniversityBeijing102206PR China State Key Laboratory of Silicon Materials Center of Electron MicroscopySchool of Materials Science and EngineeringZhejiang UniversityHangzhou310027PR China MacDiarmid Institute for Advanced Materials and Nanotechnology School of Chemical SciencesThe University of AucklandAuckland1142New Zealand MacDiarmid Institute for Advanced Materials and Nanotechnology School of Physical and Chemical SciencesUniversity of CanterburyChristchurch8140New Zealand MacDiarmid Institute for Advanced Materials and Nanotechnology School of Fundamental SciencesMassey UniversityPalmerston North4442New Zealand

The large-scale synthesis of platinum-free electrocatalysts for the oxygen reduction reaction(ORR)remains a grand challenge.We report the large-scale production of stable and active ORR electrocatalysts based on iron,an earth-abundant element.A core–shell zeolitic imidazolate framework–tannic acid coordination polymer composite(ZIF-8@K-TA)was utilized as the catalyst precursor,which was transformed into iron atoms dispersed in hollow porous nitrogen-doped carbon capsules(H-Fe-N_(x)-C)through ion exchange and pyrolysis.H-Fe-N_(x)-C fea-tures site-isolated single-atom iron centers coordinated to nitrogen in graphitic layers,high levels of nitrogen doping,and high permeability to incoming gases.Benefiting from these characteristics,H-Fe-N_(x)-C demonstrated efficient electrocatalytic activity(E_(1/2)=0.92 v,vs.RHE)and stability towards the ORR in both alkaline and acidic media.In ORR performance,it surpassed the majority of recently reported Fe-N-C catalysts and the standard Pt/C catalyst.In addition,H-Fe-N_(x)-C showed outstanding tolerance to methanol.

关键词： Metal single atoms Hollow carbon capsules Oxygen reduction reaction Metal–organic framework Electrocatalysis

Evaluating the Impacts of Using Different Digital Surface Models to Estimate Forest Height with TanDEM-X Interferometric Coherence Data

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雷达学报（中英文） 2020年第2期9卷 386-398页

作者： CHEN Hao HILL David A. WHITE Joanne C. CLOUDE shane R. Canadian Forest Service 506 Burnside Road WestVictoriaBritish ColumbiaV8Z 1M5Canada Applied Electromagnetics Consultants 26 Westfield AvenueCuparFifeKY155AAUK

In our previous studies, we demonstrated the usefulness of TanDEM-X interferometric bistatic mode with single polarization to obtain forest heights for the purposes of large area mapping. A key feature of our approach has been the use of a simplified Random volume Over Ground(RvOG) model that locally estimates forest height. The model takes TanDEM-X interferometric coherence amplitude as an input and uses an external Digital Surface Model(DSM) to account for local slope variations due to terrain topography in order to achieve accurate forest height estimation. The selection of DSM for use as a local slope reference is essential, as an inaccurate DSM will result in less accurate terrain-correction and forest height estimation. In this paper, we assessed TanDEM-X height estimates associated with scale variations in different DSMs used in the model over a remote sensing supersite in Petawawa, Canada. The DSMs used for assessments and comparisons included ASTER GDEM, ALOS GDSM, airborne DRAPE DSM, Canadian DSM and TanDEM-X DSM. Airborne Laser Scanning(ALS) data were used as reference for terrain slope and forest height comparisons. The results showed that, with the exception of the ASTER GDEM, all DSMs were sufficiently accurate for the simplified RvOG model to provide a satisfactory estimate of stand-level forest height. When compared to the ALS 95th height percentile, the modeled forest heights had R2 values greater than 80% and Root-Mean-Square Errors(RMSE)less than 2 m. For a close similarity in slope estimation with the ALS reference, coverage across Canada and open data access, the 0.75 arc-second(20 m) resolution Canadian DSM was selected as a preferred choice for the simplified RvOG model to provide TanDEM-X height estimation in Canada.

关键词： Interferometric COA Digital surface model Forest height

Wavelength stability in a hybrid photonic crystal laser through controlled nonlinear absorptive heating in the reflector

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Light(Science & Applications) 2018年第1期7卷 654-660页

作者： Andrei P.Bakoz Alexandros A.Liles Alfredo A.Gonzalez-Fernandez Tatiana Habruseva Changyu Hu Evgeny A.viktorov Stephen P.hegarty Liam O’Faolain Centre for Advanced Photonics and Process Analysis&Department of Physical Sciences Cork Institute of TechnologyCork T12P928Ireland Tyndall National Institute University College CorkLee MaltingsDyke ParadeCork T12R5CPIreland School of Physics&Astronomy University of St AndrewsNorth HaughSt Andrews KY169SSUK National Research University of Information Technologies Mechanics and OpticsSaint Petersburg 199034Russia IMEC Department of Information Technology(INTEC)Photonics Research GroupGhent UniversityTechnologiepark-Zwijnaarde 159052 GhentBelgium National Institute of Astrophysics Optics and Electronics72840 TonantzintlaMexico

The need for miniaturized,fully integrated semiconductor lasers has stimulated significant research efforts into realizing unconventional configurations that can meet the performance requirements of a large spectrum of applications,ranging from communication systems to sensing.We demonstrate a hybrid,silicon photonicscompatible photonic crystal(PhC)laser architecture that can be used to implement cost-effective,high-capacity light sources,with high side-mode suppression ratio and milliwatt output output powers.The emitted wavelength is set and controlled by a silicon PhC cavity-based reflective filter with the gain provided by a Ⅲ–Ⅴ-based reflective semiconductor optical amplifier(RSOA).The high power density in the laser cavity results in a significant enhancement of the nonlinear absorption in silicon in the high Q-factor PhC resonator.The heat generated in this manner creates a tuning effect in the wavelength-selective element,which can be used to offset external temperature fluctuations without the use of active cooling.Our approach is fully compatible with existing fabrication and integration technologies,providing a practical route to integrated lasing in wavelength-sensitive schemes.

关键词： amplifier tuning nonlinear