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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez daniel Refai Gerald R.Rodts Christian Mustroph david Gimbel Jonathan Grossberg daniel L.Barrow Matthew F.Gary Ali M.Alawieh department of Neurosurgery Emory University School of MedicineAtlantaGAUSA department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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

Stability and transferability assessment of the cotton fiber strength QTL qFS-c7-1 on chromosome A07

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The Crop Journal 2021年第2期9卷 380-386页

作者： david d.Fang Linghe Zeng Gregory N.Thyssen Christopher d.delhom Efrem Bechere don C.Jones Ping Li Cotton Fiber Bioscience Research Unit USDA-ARS-SRRCNew OrleansLA 70124USA Crop Genetics Research Unit USDA-ARSStonevilleMS 38776USA Cotton Chemistry&Utilization Unit USDA-ARS-SRRCNew OrleansLA 70124USA Cotton Structure and Quality Research Unit USDA-ARS-SRRCNew OrleansLA 70124USA Cotton Incorporated CaryNC 27513USA

Previously we identified a major cotton fiber strength QTL(qFS-c7-1)on chromosome A07 using a multiparent advanced generation intercross(MAGIC)*** assess the stability and transferability of this QTL and its utility in cotton breeding,we made ten new *** populations were developed from crosses between MAGIC recombinant inbred lines,or between cotton cultivars that are different from the MAGIC parents.A total of 2801 F_(2) plants were grown and their fiber quality traits were *** also selected a subset of F_(3) seeds from two populations,and grew F_(3) progeny plots to further evaluate the stability of this *** results showed that the peak of qFS-c7-1 is at 70–72 Mb *** QTL had a major effect on fiber strength explaining 21.9%phenotypic *** effect on other fiber quality attributes such as micronaire,short fiber content,length and uniformity varied between populations,and no effect on fiber elongation was *** QTL effects were stable in the populations analyzed,and in different generations of the same *** SSR and SNP markers near and within the QTL peak reported herein will assist selecting superior fiber quality traits in breeding,with a recommendation that the parental cotton lines should be analyzed using the seven dNA markers within the QTL peak before fully implementing marker assisted selection in a cotton breeding program.

关键词： Cotton Fiber quality Fiber strength MAGIC population qFS-c7-1

Quantitative analysis of the impact of droughts and floods on internal wars in China over the last 500 years

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Science China Earth Sciences 2017年第12期60卷 2078-2088页

作者： Harry F.LEE david d.ZHANG PEI Qing JIA Xin Ricci P.H.YUE department of Geography and International Center for China development Studies The University of Hong Kong School of Geographical Sciences Guangzhou University department of Social Sciences The Education University of Hong Kong School of Geographic and Oceanographic Sciences Nanjing University

Although many large-N quantitative studies have evidenced the adverse effects of climatic extremes on social stability in China during the historical period, most of them rely on temperature and precipitation as major explanatory variables, while the influence of floods and droughts on social crises is rarely measured. Furthermore, a comparison of the climate-society nexus among different geographic regions and at different temporal scales is missing in those studies. To address this knowledge gap,this study examines quantitatively the influence of floods and droughts on internal wars in three agro-ecological(rice, wheat,and pastoral) regions in China in Ad1470–1911. Poisson regression and wavelet transform coherence analyses are applied to allow for the non-linear and non-stationary nature of the climate-war nexus. Results show that floods and droughts are significant in driving internal wars in historical China, but are characterized by strong regional variation. In the rice region, floods trigger internal wars at the inter-annual and multi-decadal time scales. In the wheat region, both floods and droughts cause internal wars at the inter-annual and multi-decadal time scales. In the pastoral region, internal wars are associated with floods only at the multi-decadal time scale. In addition, the multi-decadal coherence between hydro-climatic extremes and internal wars in all three of the agro-ecological regions is only significant in periods in which population density is increasing or the upper limit of regional carrying capacity is being reached. The above results imply that the climate-war nexus is mediated by regional geographic factors such as physical environmental setting and population pressure. Hence, we encourage researchers who study the historical human-climate relationship to boil down data according to geographic regions in the course of statistical analysis and to examine each region individually in follow-up studies.

关键词： Floods and droughts Climatic extremes Internal wars Wars Social stability Ming-Qing period

Secure data networks for electrical distribution applications

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Journal of Modern Power Systems and Clean Energy 2015年第3期3卷 447-455页

作者： david M.LAVERTY John B.O’RAW Kang LI d.John MORROW School of EEECS Queen’s University Belfast125 Stransmillis RoadBelfast BT95AHUK

Smart Grids are characterized by the application of information communication technology(ICT)to solve electrical energy *** power networks span large geographical areas,thus a necessary component of many Smart Grid applications is a wide area network(WAN).For the Smart Grid to be successful,utilities must be confident that the communications infrastructure is *** paper describes how a WAN can be deployed using WiMAX radio technology to provide high bandwidth communications to areas not commonly served by utility communications,such as generators embedded in the distribution network.A planning exercise is described,using Northern Ireland as a case *** suitability of the technology for real-time applications is assessed using experimentally obtained latency data.

关键词： Telecoms Latency WiMAX Security

Proteomics analysis of Trichoplusia ni midgut epithelial cell brush border membrane vesicles

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Insect Science 2019年第3期26卷 424-440页

作者： Muhammad Afzal Javed Cathy Coutu david A. Theilmann Martin A. Erlandson dwayne d. Hegedus Saskatoon Research and development Centre Agriculture and Agri-Food Canada Saskatoon Saskatchewan Canada Summerland Research and development Centre Agriculture and Agri-Food Canada Summerland British Columbia Canada department of Food & Bio-Product Sciences University of Saskatchewan Saskatoon Saskatchewan Canada

The insect midgut epithelium is composed of columnar, goblet, and regenerative cells. Columnar epithelial cells are the most abundant and have membrane protrusions that form the brush border membrane (BBM) on their apical side. These increase surface area available for the transport of nutrients, but also provide opportunities for interaction with xenobiotics such as pathogens, toxins and host plant allelochemicals. Recent improvements in proteomic and bioinfbrmatics tools provided an opportunity to determine the proteome of the T. ni BBM in unprecedented detail. This study reports the identification of proteins from BBM vesicles (BBMVs) using single dimension polyacrylamide gel elec? trophoresis coupled with multi-dimensional protein identification technology. More than 3000 proteins were associated with the BBMV of which 697 were predicted to possess either a signal peptide, at least one transmembrane domain or a GPI-anchor signal. Of these, bioinfbrmatics analysis and manual curation predicted that 185 may be associated with the BBMV or epithelial cell plasma membrane. These are discussed with respect to their predicted functions, namely digestion, nutrient uptake, cell signaling, development, cell-cell interactions, and other functions. We believe this to be the most detailed proteomic analysis of the lepidopteran midgut epithelium membrane to date, which will provide information to better understand the biochemical, physiological and pathological processes taking place in the larval midgut.

关键词： brush border membrane vesicles midgut proteomic analysis Trichoplusiani

Novel Cryo-EM structures of the d1 dopamine receptor unlock its therapeutic potential

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1634-1635页

作者： david R.Sibley Kathryn d.Luderman RBenjamin Free Lei Shi Molecular Neuropharmacology Section National Institute of Neurological Disorders and StrokeIntramural Research ProgramNational Institutes of HealthBethesdaMDUSA Computational Chemistry and Molecular Biophysics Section Molecular Targets and Medications Discovery BranchNational Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA

Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the d1 dopamine receptor(dRd1)bound to either dopamine,various dRd1 agonists,or a positive allosteric modulator(PAM),while in complex with the active heterotrimeric Gs *** studies describe for the first time active-state structures of the dRd1,an exciting advancement in the field that will allow for a better understanding of selective agonist binding,dRd1 activation,G protein selectivity,and the provision of multiple templates to facilitate future drug design and discovery for this important therapeutic target.

关键词： selectivity activation potential

Need for infliximab dose intensification in Crohn's disease and ulcerative colitis

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World Journal of Gastroenterology 2014年第27期20卷 9170-9177页

作者： Carlos Taxonera david Olivares Juan L Mendoza Manuel díaz-Rubio Enrique Rey Inflammatory Bowel disease Unit Department of Gastroenterology Hospital Clínico San Carlos Instituto de Investigación del Hospital Clínico San Carlos (IdISSC) department of Gastroenterology Hospital Clínico San Carlos

AIM: To compare the need for infliximab dose intensification in two cohorts of patients with Crohn’s disease (Cd) or ulcerative colitis (UC).

关键词： Crohn's disease Ulcerative colitis Infliximab dose intensification Costs

Soil fungal and prokaryotic community structure exhibits differential short-term responses to timber harvest in the Pacific Northwest

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Pedosphere 2020年第1期30卷 109-125页

作者： Rachel E.dANIELSON Megan L.MCGINNIS Scott M.HOLUB david d.MYROLd department of Crop and Soil Science Oregon State UniversityCorvallis OR 97331-7306(USA) United State Forest Service Helena-Lewis and Clark National Forest2880 Skyway DriveHelena MT 59602(USA) Weyerhaeuser Company PO Box 275Springfield OR 97477(USA) department of Land Airand Water ResourcesUniversity of CaliforniaDavis CA 95616USA

Conventional clear-cut timber harvest is a widespread industrial practice across the Pacific Northwest;however,information regarding how these practices impact soil microbial community structure at the regional scale is *** evidence of consistent and substantial impact of harvest on soil microbial functional profiles across the region(despite a range of environmental conditions),the objective of this study was to determine the extent to which harvest also influences the structure of prokaryotic and fungal soil microbial communities,and how generalized these trends are throughout the geographic *** soil samples were collected one year before and after harvest across nine second-growth douglas-fir forests in the Pacific *** community dNA was extracted from the soils,and high-throughput targeted gene sequencing of the 16 S r RNA gene for prokaryotes and the internal transcribed spacer(ITS)gene for fungi was *** diversity was consistently and significantly higher after harvest;it was moderately so for fungal communities(+14.6%),but only marginally so for prokaryotic communities(+2.0%).Similarly,on average,a greater proportion of the variation in the community structure of fungi(20.1%)at each site was associated with forest harvest compared to that of prokaryotes(13.2%).Overall,the greatest influence of timber harvest on soil microbial communities appeared to be a relative depletion of ectomycorrhizal fungi,with a concomitant enrichment of saprotrophic *** the short-term responses of soil microbial communities across the region,particularly those of tree root-associated symbionts,may aid our understanding of the role soil microbial communities play in ecological succession.

关键词： clear-cut douglas-fir forest ectomycorrhizal fungi forest soil microbial community microbial diversity root-associated symbiont saprotrophic fungi