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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George d.Bittner department of Molecular Biosciences University of Texas at AustinAustinTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak dale R.Sengelaub George d.Bittner department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Application of Electrical Resistivity and Chargeability data on a GIS Platform in delineating Auriferous Structures in a deeply Weathered Lateritic Terrain, Eastern Cameroon

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International Journal of Geosciences 2012年第5期3卷 960-971页

作者： Albert nih Fon Vivian Bih Che Cheo Emmanuel Suh Economic Geology Unit Department of Geology Faculty of Science University of Buea Buea Cameroon Remote Sensing Unit Department of Geology Faculty of Science University of Buea Buea Cameroon

Exploration for primary gold in tropical settings is often problematic because of deep weathering and the development of a thick soil cover. In this paper we present the results of both chargeability and resistivity surveys carried out over the Belikombone hill gold prospect (14?00' - 14?25'E, 5?25' - 6?00'N) in the Betare Oya area (eastern Cameroon), where previous soil sampling had identified gold anomalies. The geophysical data were obtained using Syscal Junior 48 resistivity meter and the Schlumberger configuration array for both the vertical electrical soundings (VES) and horizontal profiling. These data were further built into a GIS framework and the continuity of favourable gold-bearing structures at depth modeled using WINSEV, REd2INV and SURFER extensions softwares. IP (Induced Polarization)-chargeability and resistivity data combined, have identified irregular anomalous zones trending NE-SW. This trend is consistent with the attitude of most auriferous quartz veins exposed in artisanal pits and parallel to the regional shear zone system and foliations. The high resistivity anomalies correspond to quartz veins while the relatively high IP anomalies correspond to low sulphide ± gold concentrations in the quartz veins. Modeling IP-chargeability and resistivity data prepared as contours and 3d maps, culminated to the development of an inferred, irregular and discontinuous mineralized body at depths of up to 95 m. The size and shape of this mineralized body can only later be tested by drilling to ascertain the resource.

关键词： Gold Exploration Tropical Settings deep Weathering IP-Chargeability and Resistivity Betare Oya 3d Maps Cameroon

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Status of autoimmune diabetes 20-year after generation of BdC2.5-TCR transgenic non-obese diabetic mouse

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World Journal of diabetes 2013年第4期4卷 88-91页

作者： Lourdes Ramirez abdel Rahim A Hamad department of Pathology Johns Hopkins University School of Medicine

Type 1 diabetes(T1d) is an autoimmune disease that results from the destruction of insulin-producing cells by autoreactive T cells,leading to lifelong dependency on insulin therapy and increased risk of long-term cardiovascular *** we take the opportunity of the 20thanniversary of the generation of the BdC2.5 TCR transgenic non-obese diabetic(NOd) mouse model,to provide a brief overview of the significant progress that has been made in understanding the role of T cells in the disease pathogenesis *** included development of hundreds of reagents that block or even reverse new-onset disease by directly or indirectly controlling T *** also reflect on the sobering fact that none of these strategies has shown significant efficacy in clinical trials and discuss potential reasons hindering translation of the preclinical findings into successful therapeutic strategies and potential ways forward.

关键词： Autoimmune diabetes Immunotherapy T cells BdC2.5 T cells Anti-Cd3 Immunosuppression

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Current understandings of the pathogenesis of type 1 diabetes:Genetics to environment

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World Journal of diabetes 2020年第1期11卷 13-25页

作者： Adebola Matthew Giwa Rizwan Ahmed Zahra Omidian Neha Majety Kagan Ege Karakus Sarah M Omer Thomas donner abdel Rahim A Hamad department of Pediatrics Johns Hopkins Medical CenterBaltimoreMD 21287United States department of Pathology Johns Hopkins Medical CenterBaltimoreMD 21205United States School of Medicine Koc UniversityIstanbul 34450Turkey department of Medicine Johns Hopkins University School of MedicineBaltimoreMD 21205United States

Type 1 diabetes(T1d)is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any *** is caused by autoreactive T cells that destroy insulin-producing beta cells in the *** studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5%annually *** daily responsibility,clinical management,and vigilance required to maintain blood sugar levels within normal range and avoid acute complications(hypoglycemic episodes and diabetic ketoacidosis)and long term micro-and macro-vascular complications significantly affects quality of life and public health care *** the expansive impact of T1d,research work has accelerated and T1d has been intensively investigated with the focus to better understand,manage and cure this *** advances have been made in the past decades in this regard,but key questions remain as to why certain people develop T1d,but not others,with the glaring example of discordant disease incidence among monozygotic *** this review,we discuss the field’s current understanding of its pathophysiology and the role of genetics and environment on the development of *** examine the potential implications of these findings with an emphasis on T1d inheritance patterns,twin studies,and disease *** a better understanding of this process,interventions can be developed to prevent or halt it at early stages.

关键词： Type 1 diabetes genetics Type 1 diabetes epigenetics Role of genetics in type 1 diabetes diabetes prevention Type 1 diabetes environment Type 1 diabetes twin studies Type 1 diabetes concordance Type 1 diabetes discordance

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Translational Bioinformatics: Past, Present, and Future

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Genomics, Proteomics & Bioinformatics 2016年第1期14卷 31-41页

作者： Jessica d.Tenenbaum department of Biostatistics and Bioinformatics Duke University School of Medicine

Though a relatively young discipline, translational bioinformatics （TBI） has become a key component of biomedical research in the era of precision medicine. development of high-throughput technologies and electronic health records has caused a paradigm shift in both healthcare and biomedical research. Novel tools and methods are required to convert increasingly voluminous datasets into information and actionable knowledge. This review provides a definition and contex- tualization of the term TBI, describes the discipline＇s brief history and past accomplishments, as well as current loci, and concludes with predictions of future directions in the field.

关键词： Translational bioinformatics Biomarkers Genomics Precision medicine Personalized medicine

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Challenges in Understanding Genome-Wide dNA Methylation

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Journal of Computer Science & Technology 2010年第1期25卷 26-34页

作者：张伟奇 Andrew d. Smith Cold Spring Harbor Laboratory Cold Spring Harbor Bioinformatics division TNLIST and MOE Key Lab of Bioinformatics Tsinghua University department of Biological Sciences University of Southern California

dNA methylation is a chemical modification of the bases in genomes. This modification, most frequently found at CpG dinucleotides in eukaryotes, has been identified as having multiple critical functions in broad and diverse species of animals and plants, while mysteriously appears to be lacking from several other well-studied species. dNA methylation has well known and important roles in genome stability and defense, its pattern change highly correlates with gene regulation. Much evidence has linked abnormal dNA methylation to human diseases. Most prominently, aberrant dNA methylation is a common feature of cancer genomes. Elucidating the precise functions of dNA methylation therefore has great biomedical significance. Here we provide an update on large-scale experimental technologies for detecting dNA methylation on a genomic scale. We also discuss new prospect and challenges that computational biologist will face when analyzing dNA methylation data.

关键词： dNA methylation epigenome computational epigenomics

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Estimation of the density of neural,glial,and endothelial lineage cells in the adult mouse dentate gyrus

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Neural Regeneration Research 2022年第6期17卷 1286-1292页

作者： Joshua d.Rieskamp Patricia Sarchet Bryon M.Smith Elizabeth d.Kirby Neuroscience Graduate Program The Ohio State UniversityColumbusOHUSA department of Psychology The Ohio State UniversityColumbusOHUSA department of Neuroscience The Ohio State UniversityColumbusOHUSA Chronic Brain Injury Program The Ohio State UniversityColumbusOHUSA

The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong *** regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust estimations of adultborn versus pre/perinatally-born neuron *** contrast,the non-neurogenic functions of adult neural stem cells and their immediate progeny,such as secretion of bioactive growth factors and expression of extracellular matrix-modifying proteins,lack similar framing due to few estimates of their number versus other prominent secretory ***,we apply immunohistochemical methods to estimate cell density of neural stem/progenitor cells versus other major classes of glial and endothelial cell types that are potentially secretory in the dentate gyrus of adult *** the cell types quantified,we found that GFAP^(+)SOX2^(+)stellate astrocytes were the most numerous,followed by Cd31^(+)endothelia,GFAP-SOX2^(+)intermediate progenitors,Olig2^(+)oligodendrocytes,Iba1+microglia,and GFAP^(+)SOX2^(+)radial glia-like neural stem *** did not observe any significant sex differences in density of any cell ***,neural stem/progenitor cells were present at a similar density as several cell types known to have potent functional roles via their *** findings may be useful for refining hypotheses regarding the contributions of these cell types to regulating hippocampal function and their potential therapeutic *** experimental protocols were approved by the Ohio State University Institutional Animal Care and Use Committee(protocol#2016A00000068)on July 14,2016.

关键词： adult neurogenesis dentate gyrus endothelia glia hippocampus neural stem cell secretome stereology

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Effects of symmetric and asymmetric salt conditions on a selective solid-state nanopore assay

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Nano Research 2022年第11期15卷 9936-9942页

作者： Ian d.Wadsworth Adam R.Hall Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences Wake Forest School of MedicineWinston-SalemNC 27101USA Comprehensive Cancer Center Wake Forest School of MedicineWinston-SalemNC 27157USA

Conventional solid-state nanopore measurements sense all translocating entities,necessitating meticulous analysis to differentiate target *** address this,we have established a selective assay with the platform that has shown utility in quantifying several nucleic acid ***,limited detection efficiency and intrinsic noise have so far limited assay resolution to 10 *** in this value require manipulation of translocation ***,we report the effects of NaCl conditions on assay *** first investigate symmetric conditions,finding sensitivity increases with salt concentration but selectivity is maximized at 1.0 M *** then probe asymmetric conditions,showing a remarkable impact on assay sensitivity and selectivity when measurement buffer NaCl concentration in the reservoir with the translocating molecules is low and the opposite reservoir is *** optimum conditions,we demonstrate detection of target biomolecules down to a concentration of 100 pM which is an improvement of 2 orders of magnitude over past results.

关键词： solid-state nanopores biomarkers amplification-free detection salt gradient nucleic acids

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The Chinese skeleton: insights into microstructure that help to explain the epidemiology of fracture

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Bone Research 2014年第2期2卷 80-92页

作者： Elaine Cong Marcella d Walker New York Presbyterian Hospital

Osteoporotic fractures are a major public health problem worldwide, but incidence varies greatly across racial groups and geographic regions. Recent work suggests that the incidence of osteoporotic fracture is rising among Asian populations. Studies comparing areal bone mineral density and fracture across races generally indicate lower bone mineral density in Asian individuals including the Chinese, but this does not reflect their relatively low risk of non-vertebral fractures. In contrast, the Chinese have relatively high vertebral fracture rates similar to that of Caucasians. The paradoxically low risk for some types of fractures among the Chinese despite their low areal bone mineral density has been elucidated in part by recent advances in skeletal imaging. New techniques for assessing bone quality non-invasively demonstrate that the Chinese compensate for smaller bone size by differences in hip geometry and microstructural skeletal organization. Studies evaluating factors influencing racial differences in bone remodeling, as well as bone acquisition and loss, may further elucidate racial variation in bone microstructure. Advances in understanding the microstructure of the Chinese skeleton have not only helped to explain the epidemiology of fracture in the Chinese, but may also provide insight into the epidemiology of fracture in other races as well.

关键词： bone insights into microstructure that help to explain the epidemiology of fracture The Chinese skeleton

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