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The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

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Frontiers in Biology 2017年第2期12卷 124-138页

作者： gregory w. kirschen Hanxiao Liu Tracy Lang Xuelin Liang Shaoyu Ge Qiaojie Xiong Medical Scientist Training Program (MSTP) Stony Brook University Stony Brook NY 11794 USA Molecular & Cellular Pharmacology Program Stony Brook University Stony Brook NY 11794 USA Department of Neurobiology & Behavior Stony Brook University Stony Brook NY 11794 USA Simons Summer Research Program (SSRP)

BACKGROUND： Neuronal primary cilia are sensory organelles that are critically involved in the proper grow.h, development, and function of the central nervous system （CNS）. Recent w.rk also suggests that they signal in the context of CNS injury, and that abnormal ciliary signaling may be implicated in neurological diseases. METHODS： w. quantified the distribution of neuronal primary cilia alignment throughout the normal adult mouse brain by immunohistochemical staining for the primary cilia marker adenylyl cyclase Ⅲ （ACⅢ） and measuring the angles of primary cilia w.th respect to global and local coordinate planes. w. then introduced tw. different models of acute brain insult--temporal lobe seizure and cerebral ischemia, and re-examined neuronal primary cilia distribution, as w.ll as ciliary lengths and the proportion of neurons harboring cilia. RESULTS： Under basal conditions, cortical cilia align themselves radially w.th respect to the cortical surface, w.ile cilia in the dentate gyms align themselves radially w.th respect to the granule cell layer. Cilia of neurons in the striatum and thalamus, by contrast, exhibit a w.de distribution of ciliary arrangements. In both cases of acute brain insult, primary cilia alignment w.s significantly disrupted in a region-specific manner, w.th areas affected by the insult preferentially disrupted. Further, the tw. models promoted differential effects on ciliary lengths, w.ile only the ischemia model decreased the proportion of ciliated cells. CONCLUSIONS： These findings provide evidence for the regional anatomical organization of neuronal primary cilia in the adult brain and suggest that various brain insults may disrupt this organization.

关键词： cerebral cortex dentate gyrus temporal lobe seizure cerebral ischemia

Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： Andrew.gregory Chengyun Tang Fan Fan Department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,w.th projections indicating a substantial increase in affected individuals due to the aging global *** the w.rld Health Organization,AD/ADRD has affected more than 55 million individuals w.rldw.de,w.th an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

Primary cilia as a novel horizon betw.en neuron and environment

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Neural Regeneration Research 2017年第8期12卷 1225-1230页

作者： gregory w.kirschen Qiaojie Xiong Medical Scientist Training Program Stony Brook University Stony Brook NY USA Department of Neurobiology & Behavior Stony Brook University Stony Brook NY USA

The primary cilium, a hair-like sensory organelle found on most mammalian cells, has gained recent attention w.thin the field of neuroscience. Although neural primary cilia have been know. to play a role in embryonic central nervous system patterning, w. are just beginning to appreciate their importance in the mature organism. After several decades of investigation and controversy, the neural primary cilium is emerging as an important regulator of neuroplasticity in the healthy adult central nervous system. Further, primary cilia have recently been implicated in disease states such as cancer and epilepsy. Intriguingly, w.ile primary cilia are expressed throughout the central nervous system, their structure, receptors, and signaling pathw.ys vary by anatomical region and neural cell type. These differences likely bear relevance to both their homeostatic and neuropathological functions, although much remains to be uncovered. In this review. w. provide a brief historical overview.of neural primary cilia and highlight several key advances in the field over the past few.decades. w. then set forth a proposed research agenda to fill in the gaps in our know.edge regarding how.the primary cilium functions and malfunctions in nervous tissue, w.th the ultimate goal of targeting this sensory structure for neural repair follow.ng injury.

关键词： G protein-coupled receptor sonic hedgehog seizure stroke stem cell neurogenesis plasticity

A functional tacrolimus-releasing nerve w.ap for enhancing nerve regeneration follow.ng surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.w.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration follow.ng surgical nerve repair is slow.and often incomplete,resulting in poor functional recovery w.ich sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outw.igh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,w.th suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery w.th minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve w.ap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the w.ap degrades w.thin 120 days into biocompatible *** released from the nerve w.ap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models w.ile off-target systemic drug exposure is reduced by 80%compared w.th systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve w.ap tacrolimus

ADAM10 facilitates rapid neural stem cell cycling and proper positioning w.thin the subventricular zone niche via JAMC/RAP1Gap signaling

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Neural Regeneration Research 2022年第11期17卷 2472-2483页

作者： Nadia McMillan gregory w.kirschen Sanket Desai Emma Xia Stella E.Tsirka Adan Aguirre Program in Neuroscience and Medical Scientist Training Program Renaissance School of Medicine at Stony Brook UniversityStony BrookNYUSA Department of Pharmacological Sciences Renaissance School of Medicine at Stony Brook UniversityStony BrookNYUSA Department of Neurology Beth Israel Deaconess Medical Center/Harvard Medical SchoolBostonMAUSA Department of Gynecology and Obstetrics Johns Hopkins HospitalBaltimoreMDUSA

The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs w.thin diffe rent domains of the adult neural stem cell niche,the subventricular zone are not w.ll *** NSCs are arranged at the apical ventricular w.ll,w.ile mitotically activated NSCs are found in the basal,vascular region of the subventricular ***,w. found that ADAM 10(a disintegrin and metalloproteinase 10)is essential in NSC association w.th the ventricular w.ll,and via this adhesion to the apical domain,ADAM10 regulates the sw.tch from quiescent and undiffe rentiated NSC to an actively prolife rative and differentiating cell *** of JAMC(junctional adhesion molecule C)by ADAM 10 increases Rap1 GAP *** molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage *** the molecular mechanisms responsible for regulating the proper positioning of NSCs w.thin the subventricular zone niche and lineage progression of NSCs could provide new.targets for drug development to enhance the regenerative prope rties of neural tissue.

关键词： ADAM10 adhesion junctional adhesion molecule C neural stem cells neurogenesis olfactory bulb Rap1Gap sub-ventricular zone

Quantizing Euclidean Motions via Double-Coset Decomposition

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Research 2019年第1期2019卷 525-540页

作者： Christian w.lker Sipu Ruan gregory S.Chirikjian Johns Hopkins University BaltimoreMDUSA Department of Mechanical Engineering National University of SingaporeSingapore

Concepts from mathematical crystallography and group theory are used here to quantize the group of rigid-body motions,resulting in a“motion alphabet”w.th w.ich robot motion primitives are *** these primitives it is possible to develop a dictionary of physical *** w.th an alphabet of the sort developed here,intelligent actions of robots in the w.rld can be approximated w.th fnite sequences of characters,thereby forming the foundation of a language in w.ich robot motion is *** particular,w. use the discrete handedness-preserving symmetries of macromolecular crystals(know. in mathematical crystallography as Sohncke space groups)to form a coarse discretization of the space SE(3)of rigid-body *** discretization is made fner by subdividing using the concept of double-coset *** specifcally,a very efcient,equivolumetric quantization of spatial motion can be defned using the group-theoretic concept of a double-coset decomposition of the formΓ\SE(3)/Δ,w.ereΓis a Sohncke space group andΔis a fnite group of rotational symmetries such as those of the *** resulting discrete alphabet is based on a very uniform sampling of SE(3)and is a tool for describing the continuous trajectories of robots and *** efcient coarse-to-fne search algorithm is presented to round of any motion sampled from the continuous group of motions to the nearest element of our *** is show. that our alphabet and this efcient rounding algorithm can be used as a geometric data structure to accelerate the performance of other sampling schemes designed for desirable dispersion or discrepancy ***,the general“signals to symbols”problem in artifcial intelligence is cast in this framew.rk for robots moving continuously in the w.rld.

关键词： robot primitive thereby

Advancements in the mind-machine interface:tow.rds re-establishment of direct cortical control of limb movement in spinal cord injury

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Neural Regeneration Research 2016年第7期11卷 1060-1061页

作者： Jian Guan gregory w.J.Haw.yluk Department of Neurosurgery Clinical Neurosciences CenterUniversity of Utah

Spinal cord injury（SCI）resulting in loss of motor function can be caused by a variety of conditions,ranging from traumatic to neoplastic to *** is estimated that nearly 300,000individuals live w.th the effects of SCI in the United States alone（National Spinal Cord Injury Statistical Center,2016）.Current treatment modalities for patients suffering from SCI are primarily supportive,

关键词： cortical modalities neoplastic alone traumatic restoration suffering cortex options infectious

Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate

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Neural Regeneration Research 2016年第6期11卷 882-885页

作者： Christian A.Bow.rs Bornali Kundu gregory w.J.Haw.yluk Department of Neurosurgery Clinical Neurosciences Center University of Utah

Follow.ng publication of NASCIS Ⅱ, methylprednisolone sodium succinate（MPSS） w.s hailed as a breakthrough for patients w.th acute spinal cord injury（SCI）. MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and w. review.our recent findings w.ich reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. w. discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions w.ich have evolved. As science has failed to resolve the MPSS debate w. argue that the debate is an increasingly philosophical one. w. question w.ether SCI might be view.d as a serious condition like cancer w.ere serious side effects of therapeutics are tolerated even w.en benefits may be small. w. also draw.attention to the similarity betw.en the side effects of MPSS and isotretinoin w.ich is prescribed for the cosmetic disorder acne vulgaris. Ultimately w. question how.patient autonomy should be w.ighed in the context of current SCI guidelines and MPSS＇s status as a historical standard of care.

关键词： debate autonomy opinion argue break informed administration translational historical preference

Optical monitoring of particle aggregates

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Journal of Environmental Sciences 2009年第1期21卷 2-7页

作者： John gregory Department of Civil Environmental and Geomatic EngineeringUniversity College London

Methods for monitoring particle aggregation are briefly review.d. Most of the techniques are based on some form of light scattering and may be greatly dependent on the optical properties of aggregates, w.ich are not generally know.. As fractal aggregates grow.larger their density can become very low.and this has important practical consequences for light scattering. For instance, the scattering coefficient may be much less than for solid objects, w.ich means that the aggregates can appear much smaller than their actual size by a light transmission method. Also, for low.density objects, a high proportion of the scattered light energy is w.thin a small angle of the incident beam, w.ich may also be relevant for measurements w.th aggregates. Using the ＂turbidity fluctuation＂ technique as an example, it is show. how.the apparent size of hydroxide flocs depends mainly on the included impurity particles, rather than the hydroxide precipitate itself. Results using clay suspensions w.th hydrolyzing coagulants and polymeric floceulants under different string conditions are discussed.

关键词： monitoring method flocculation turbidity fluctuation