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Facilitating transparency in spinal cord injury studies using data standards and ontologies

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Neural Regeneration Research 2014年第1期9卷 6-7页

作者： vance p.lemmon Saminda Abeyruwan Ubbo Visser John L.Bixby Department of Neurological Surgery University of Miami Miami project to Cure paralysis University of Miami Center for Computational Science University of Miami Department of Computer Science University of Miami Molecular&Cellular pharmacology University of Miami

progress in developing robust therapies for spinal cord injury （SCI）, trau- matic brain injury （TBI） and peripheral nerve injury has been slow. A great deal has been learned over the past 30 years regarding both the intrinsic factors and the environmental factors that regulate axon growth, but this large body of information has not yet resulted in clinically available thera- peutics. This therapeutic bottleneck has many root causes, but a consensus is emerging that one contributing factor is a lack of standards for experi- mental design and reporting. The absence of reporting standards, and even of commonly accepted definitions of key words, also make data mining and bioinformatics analysis of neural plasticity and regeneration difficult, if not impossible. This short review will consider relevant background and poten- tial solutions to this problem in the axon regeneration domain.

关键词： data Facilitating transparency in spinal cord injury studies using data standards and ontologies SCI

Exploiting kinase polypharmacology for nerve regeneration

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Neural Regeneration Research 2016年第1期11卷 71-72页

作者： Hassan Al-Ali John L.Bixby vance p.lemmon Miami project to Cure paralysis University of Miami Center for Computational Science University of Miami Department of Neurological Surgery University of Miami Department of Molecular & Cellular pharmacology University of Miami

The human central nervous system（CNS）has a markedly poor capacity for regenerating its axons following *** appears to be due to two main causes：1）a developmentally regulated decline in regenerative capacity within mature CNS neurons,and 2）the presence of biological components that constitute barriers to axon regeneration（e.g.,growth-inhibitory molecules）.

关键词： regeneration alterations mature markedly constitute regenerative barriers phenotypic similarity inhibit

Casein kinase signaling in axon regeneration

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Neural Regeneration Research 2016年第2期11卷 210-211页

作者： Nagi G.Ayad Jae K.Lee vance p.lemmon The Center for Therapeutic Innovation The Miami Project to Cure Paralysis Department of Psychiatry and Behavioral SciencesUniversity of Miami The Miami project to Cure paralysis Department of NeurosurgeryUniversity of Miami

Recent studies suggest that cell cycle pathways may contain therapeutic targets important for *** example of this is the finding that the vertebrate cell cycle exploits proteolysis pathways,yet these activities persist in fully differentiated cells that have exited the cell cycle such as *** have known for some time that a ubiquitin ligase.

关键词： ApC Casein kinase signaling in axon regeneration

Genetically modifying transcription factors to promote CNS axon regeneration

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Neural Regeneration Research 2017年第5期12卷 737-738页

作者： Saloni T.Mehta John L.Bixby vance p.lemmon Miami project to Cure paralysis University of Miami Miller School of Medicine Miami FL USA Center for Computational Science University of Miami Miller School of Medicine Miami FL USA Neurological Surgery University of Miami Miller School of Medicine Miami FL USA Molecular & Cellular pharmacology University of Miami Miller School of Medicine Miami FL USA

Following injury to the central nervous system（CNS）,severed axons fail to regenerate and re-form functional ***,CNS neurons appear to lack the intrinsic ability to modify their gene expression patterns to activate a robust regenerative response,perhaps as a result of limited plasticity in the adult brain（Davis,2013）.On the other hand,

关键词： CNS gene Jun Vp

Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

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Neural Regeneration Research 2016年第1期11卷 144-149页

作者： Matt C.Danzi Dario Motti Donna L.Avison John L.Bixby vance p.lemmon The Miami project to Cure paralysis University of MiamiLois Pope LIFE Center Department of Surgery Leonard M. Miller School of Medicine University of Miami Department of Neurological Surgery University of Miami Department of Molecular and Cellular pharmacology University of Miami

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

关键词： acetaminophen analgesics axon buprenorphine dorsal root ganglia gene expression peripheral nerve injuries regeneration sciatic nerve wound healing

AAV8 transduction capacity is reduced by prior exposure to endosome-like pH conditions

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Neural Regeneration Research 2021年第5期16卷 851-855页

作者： Jeffrey ALowell Kar Men Mah John LBixby vance plemmon Miami project to Cure paralysis University of MiamiMiamiFLUSA Department of Neurological Surgery University of MiamiMiamiFLUSA Department of Molecular and Cellular pharmacology University of MiamiMiamiFLUSA

Adeno-associated virus(AAV)is an essential instrument in the neuroscientist’s toolkit,which allows delivery of DNA to provide labeling with fluorescent proteins or genetic instructions to regulate gene *** the field of neural regeneration,the transduction of neurons enables the observation and regulation of axon growth and regeneration,and in the future will likely be a mechanism for delivering molecular therapies to promote sprouting and regeneration after central nervous system *** formulations of AAV preparations permit efficient viral transduction under physiologic conditions,but an improved understanding of the mechanistic limitations of AAV transduction may facilitate production of more resilient AAV strains for investigative and therapeutic *** studied AAV transduction in the context of prior exposure of AAV serotype 8(AAV8)to environmental pH within the range encountered during endosomal endocytosis(pH 7.4 to pH 4.4),during which low pH-triggered structural and autoproteolytic changes to the viral capsid are believed to be necessary for endosome escape and virus *** to the fundamental nature of these processes,we hypothesized that premature exposure of AAV8 particles to acidic pH would decrease viral transduction of HT1080 cells in vitro,as measured by fluorescent reporter gene expression using high-content imaging *** found that increasingly acidic incubation conditions were associated with concomitant reductions in transduction efficiency,and that quantitative levels of reporter gene expression in transduced cells were similarly *** biggest decrease in transduction occurred between pH 7.4 and pH 6.4,suggesting the possible co-occurrence of a pH-associated event and viral inactivation within that *** together,these findings indicate that exposure of AAV8 to acidic pH for as little as 1 hour is deleterious to transduction *** studies are necessary to understand the pH-associated

关键词： adeno-associated virus autolytic capsid low pH protease proteolytic temperature trafficking transduction viral inactivation