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Regulation of neuronal bioenergetics as a therapeutic strategy in neurodegenerative diseases

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Neural Regeneration Research 2021年第8期16卷 1467-1482页

作者： Isaac G.Onyango james P.bennett Gorazd b.Stokin Center for Translational Medicine International Clinical Research Centre(ICRC)St.Anne’s University HospitalBrnoCzech Republic Neurodegeneration Therapeutics 3050A Berkmar DriveCharlottesvilleVAUSA

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a heterogeneous group of debilitating disorders with multifactorial etiologies and pathogeneses that manifest distinct molecular mechanisms and clinical manifestations with abnormal protein dynamics and impaired bioenergetics. Mitochondrial dysfunction is emerging as an important feature in the etiopathogenesis of these age-related neurodegenerative diseases. The prevalence and incidence of these diseases is on the rise with the increasing global population and average lifespan. Although many therapeutic approaches have been tested, there are currently no effective treatment routes for the prevention or cure of these diseases. We present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in these diseases and highlight recent advances in novel therapeutic strategies targeting neuronal bioenergetics as potential approach for treating these diseases.

关键词： aging Alzheimer's disease amyotrophic lateral sclerosis Huntington's disease mitochondrial biogenesis mitochondrial dysfunction mtDNA mutations neurodegeneration oxidative stress Parkinson's disease

Astronomical time scale for the lower Doushantuo Formation of early Ediacaran,South China

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Science bulletin 2018年第22期63卷 1485-1494页

作者： Yu Sui Chunju Huang Rui Zhang Zhixiang Wang james Ogg David b.Kemp State Key Laboratory of biogeology and Environmental Geology School of Earth SciencesChina University of GeosciencesWuhan 430074China State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Chengdu University of TechnologyChengdu 610059China Department of Earth Atmospheric and Planetary SciencesPurdue UniversityWest LafayetteIN 47907USA School of Geosciences University of AberdeenAberdeenScotland AB243UEUK

Nearly 90% of the Ediacaran Period(635–541 Ma) of the Neoproterozoic is represented by the Doushantuo Formation(DST Fm) in South *** lowest Member I is a 3.7 m-thick cap carbonate deposited at the termination of the Cryogenian Marinoan *** DST Fm consists of alternating organic-rich black shale and thinly bedded dolostone, and it contains some of the oldest records of multicellular life and three pronounced negative carbon isotope *** Jiulongwan(JLW) section is a well-studied reference section for these Ediacaran *** analysis of geochemical data through the lower DST Fm(22.3 m) shows 27 predominant ～90 cm sedimentary cycles that correspond to 405-ka long eccentricity *** power spectra of the 405-ka tuned Ca and Fe/Ti series show significant peaks at ～1.2-Ma, 405-ka, 133-ka, 128-ka, 100-ka, 82-ka, ～31-ka and 29-ka periods, respectively.A 11.16 Malong astronomical time scale has been constructed for the lower DST Fm and provide a duration of 1.6 Ma for the cap carbonate(Member Ⅰ) based on the 405-ka long eccentricity cycle *** the U-Pb age of 635.2 ± 0.6 Ma for the volcanic ash bed at the Member Ⅰ/Ⅱboundary, we proposed a 636.8 Ma age for the base of the DST *** ages and astronomical timescale provide important new constraints on the subdivision of Ediacaran strata, and have implications for understanding the character of the first negative δ^(13)C excursion(EN1).Orbital forcing may have been played an important role for the climate changes and the evolution of Ediacaran multi-cellular life and the carbon cycle variations.

关键词： Ediacaran Doushantuo Formation Astronomical time scale Orbital forcing Jiulongwan section

Time-dependent viscoelastic properties along rat small intestine

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World Journal of Gastroenterology 2005年第32期11卷 4974-4978页

作者： james b Smith Jing-bo Zhao Yan-Ling Dou Hans Gregersen Institute of Experimental Clinical Research Aarhus University Denmark Center of Excellence in Visceral biomechanics and Pain Aalborg Hospital and Center of SMI Aalborg University Aalborg Denmark Department of Gastroenterology China-Japan Friendship Hospital Beijing 100029 China

AIM： To measure the time-dependent （viscoelastic） behavior in the change of the small intestinal opening angle and to test how well the behavior could be described by the Kelvin model for a standard linear solid. METHODS： Segments from the duodenum, jejunum, and ileum were harvested from 10 female Wistar rats and the luminal diameter, wall thickness, and opening angle over time （θ（t）） were measured from rings cut from these segments. RESULTS： Morphometric variations were found along the small intestine with an increase in luminal area and a decrease in wall thickness from the duodenum to the ileum. The opening angle obtained after 60 rain was highest in the duodenum （220.8±12.9°）and decreased along the length of the intestine to 143.9±8.9° in the jejunum and 151.4±9.4° in the ileum. The change of opening angle as a function of time, fitted well to the Kelvin model using the equation θ（t）/θo = [1-ηexp （-λt）] after the ring was cut. The computed creep rate λ. did not differ between the segments. Compared to constant calculated from pig aorta and coronary artery, it showed that α agreed well （within 5%）, η was three times larger than that for vascular tissue, and λ ranged ±40% from the value of the pig coronary artery and was a third of the value of pig aorta. CONCLUSION： The change of opening angle over time for all the small intestine segments fits well to the standard linear spring-dashpot model. This viscoelastic constant of the rat small intestine is fairly homogenous along its length. The data obtained from this study add to a base set of biomechanical data on the small intestine and provide a reference state for comparison to other tissues,diseased intestinal tissue or intestinal tissue exposed to drugs or chemicals.

关键词： biomechanics Standard linear solid Creep Opening angle

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger barbara Schaedl james Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Controlling plant architecture by manipulation of gibberellicacid signalling in petunia

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Horticulture Research 2014年第1期1卷 16-21页

作者： Yin-Chih Liang Michael S reid Cai-Zhong Jiang Department of Plant Sciences University of California DavisOne Shields AvenueDavisCA 95616USA Crops Pathology&Genetics Research Unit USDA-ARSOne Shields AvenueDavisCA 95616USA

Since stem elongation is a gibberellic acid(GA)response,GA inhibitors are commonly used to control plant height in the production of potted ornamentals and bedding *** this study,we investigated interfering with GA signaling by using molecular techniques as an alternative *** isolated three putative GID1 genes(PhGID1A,PhGID1b and PhGID1C)encoding GA receptors from ***-induced gene silencing(VIGS)of these genes results in stunted growth,dark-green leaves and *** also isolated the gai mutant gene(gai-1)from *** have generated transgenic petunia plants in which the gai mutant protein is over-expressed under the control of a dexamethasone-inducible *** system permits induction of the dominant Arabidopsis gai mutant gene at a desired stage of plant development in petunia plants by the application of dexamethasone(Dex).The induction of gai in Dex-treated T1 petunia seedlings caused dramatic growth retardation with short internodes.

关键词： pet plant bedding

What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang John A.Kershaw Mark J.Ducey Yuan Sun james b.McCarter Integrated Forest Mensuration and Systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China Scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships Stand structure Volume estimation Stand-level attributes

The molecular profile of nerve repair: humans mirror rodents

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Neural Regeneration Research 2021年第7期16卷 1440-1441页

作者： Matthew b.Wilcox Kristjan R.Jessen Tom J.Quick james b.Phillips Peripheral Nerve Injury Research Unit Royal National Orthopaedic HospitalStanmoreUK Department of Pharmacology UCL School of PharmacyUniversity College LondonLondon WC1N 1AXUK UCL Centre for Nerve Engineering University College LondonLondonUK Department of Cell and Developmental biology University College LondonLondonUK

Peripheral nerve injuries(PNI)are common following blunt or penetrating trauma and can lead to disability and chronic pain in affected individuals,with limited options available to promote regeneration and functional *** animal models,it is known that the regenerative capacity of the peripheral nervous system(PNS)is heavily dependent upon the remarkable ability of Schwann cells to undergo a phenotypic shift from a supportive/myelinating/maintaining phenotype to one that encourages neural regeneration.

关键词： injuries mirror neural

Update on Molecular Imaging in Parkinson's Disease

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Neuroscience bulletin 2018年第2期34卷 330-340页

作者： Zhen-Yang Liu Feng-Tao Liu Chuan-Tao Zuo james b.Koprich Jian Wang Department of Neurology and National Clinical Research Center for Ageing and Medicine Huashan Hospital Fudan University PET Center Huashan Hospital Fudan University Krembil Institute Toronto Western Hospital University Health Network

Advances in radionuclide tracers have allowed for more accurate imaging that reflects the actions of numerous neurotransmitters, energy metabolism utilization, inflammation, and pathological protein accumulation. All of these achievements in molecular brain imaging have broadened our understanding of brain function in Parkinson’s disease(PD).The implementation of molecular imaging has supported more accurate PD diagnosis as well as assessment of therapeutic outcome and disease progression. Moreover, molecular imaging is well suited for the detection of preclinical or prodromal PD cases. Despite these advances, future frontiers of research in this area will focus on using multi-modalities combining positron emission tomography and magnetic resonance imaging along with causal modeling with complex algorithms.

关键词： Parkinson’s disease Positron emission tomography SPECT

Strigolactones and the Regulation of Pea Symbioses in Response to Nitrate and Phosphate Deficiency

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Molecular Plant 2013年第1期6卷 76-87页

作者： Eloise Foot Kaori Yoneyama Cassandra J. Hugill Laura J. Quittenden james b. reidt School of Plant Science University of Tasmania Private Bag 55 Hobart Tasmania 7001 Australia Weed Science Centre Utsunomiya University 350 Mine-machi Utsunomiya 321-8505 Japan

New roles for the recently identified group of plant hormones, the strigolactones, are currently under active investigation. One of their key roles is to regulate plant symbioses. These compounds act as a rhizosphere signal in arbuscular mycorrhizal symbioses and as a positive regulator of nodulation in legumes. The phosphorous and nitrogen status of the soil has emerged as a powerful regulator of strigolactone production. However, until now, the potential role of strigolactones in regulating mycorrhizal development and nodulation in response to nutrient deficiency has not been proven. In this paper, the role of strigolactone synthesis and response in regulating these symbioses is examined in pea （Pisum sativum L.）. Pea is well suited to this study, since there is a range of well-characterized strigolactone bio- synthesis and response mutants that is unique amongst legumes. Evidence is provided for a novel endogenous role for strigolactone response within the root during mycorrhizal development, in addition to the action of strigolactones on the fungal partner. The strigolactone response pathway that regulates mycorrhizal development also appears to dif- fer somewhat from the response pathway that regulates nodulation. Finally, studies with strigolactone-deficient pea mutants indicate that, despite strong regulation of strigolactone production by both nitrogen and phosphate, strigolac- tones are not required to regulate these symbioses in response to nutrient deficiency.

关键词： Strigolactones nodulation mycorrhizae nitrate phosphate pea.