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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

The embryology of persistent cloaca and urogenital sinus malformations

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Asian Journal of Andrology 2020年第2期22卷 124-128页

作者： david F m Thomas University of Leeds LeedsWest Yorkshire LS29JTUK

Cloacal malformations are characterized by the confluence of the lower urinary tract,the female reproductive tract,and the rectum to create a common channel with a single opening on the *** presence of a cloaca is a normal phase of early human embryological *** the 4^th and 7^th weeks of gestation,the cloaca undergoes subdivision to form the hindgut and urogenital *** of this process results in the congenital anomaly termed persistent cloaca(PC).The term urorectal septum malformation sequence(URSmS)is also used to describe this *** classic description of this process which is still cited in many standard textbooks dates from the 19th ***,this has been increasingly called into question by the findings of studies using modern scientific *** sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal *** this condition,the anorectal canal opens separately on the *** presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female ***,the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.

关键词： cloaca embryology urogenital sinus

Duplication and diversification of insulin genes in ray-finned fish

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Zoological Research 2019年第3期40卷 185-197页

作者： david m.Irwin Department of Laboratory medicine and Pathobiology University of Toronto Banting and Best Diabetes Centre University of Toronto

Insulin is a key hormone for the regulation of metabolism in *** is produced by pancreatic islet cells in response to elevated glucose levels and leads to the uptake of glucose by tissues such as liver and adipose tissue to store *** also has additional functions in regulating *** work has shown that the proglucagon gene,which encodes hormones counter regulating insulin,is duplicated in teleost fish,and that the peptide hormones encoded by these genes have diversified in function.I sought to determine whether similar processes have occurred to insulin genes in these *** of fish genomes revealed an unexpected diversity of insulin genes.A triplication of the insulin gene occurred at the origin of teleost fish,however one of these three genes,insc,has been lost in most teleost fish *** two other insulin genes,insa and insb,have been retained but show differing levels of selective constraint suggesting that they might have diversified in ***,a duplicate copy of the insa gene,which I named insab,is found in many *** coding sequenee encoded by insab genes is under weak selective constraint,with its predicted protein sequences losing their potential to be processed into a two-peptide ***,these sequences have retained perfectly conserved cystine residues,suggesting that they maintain insulin's three-dimensional structure and therefore might modulate the processing and secretion of insulin produced by the other genes.

关键词： Insulin Teleost fish Gene duplicati on Adaptive evolution Gene loss

The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin david m.Lubman Department of Surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer *** play an important role in medicine and are involved in various human disease conditions including ***-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and *** N-glycosylation significantly impacts cancer processes and targeted therapies in ***,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and *** review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and ***,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are *** and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been ***,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

motilin and ghrelin gene experienced episodic evolution during primitive placental mammal evolution

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Science China(Life Sciences) 2010年第6期53卷 677-682页

作者： IRWIN m. david Departments of Laboratory medicine and Pathobiology and the Banting and Best Diabetes Centre University of Toronto

motilin and ghrelin,members of a structure-function-related hormone family,play important roles in gastrointestinal function,regulation of energy homeostasis and growth hormone *** observed episodic evolution in both of their prehormone gene sequences during primitive placental mammal evolution,during which most of the nonsynonymous changes result in radical *** note,a functional obestatin hormone might have only originated after this episodic evolution *** in placental mammal evolution,a series of biology complexities *** the same time the motilin and ghrelin prehormone genes,which play important roles in several of these processes,experienced episodic evolution with dramatic changes in their coding *** observations suggest that some of the lineage-specific physiological adaptations are due to episodic evolution of the motilin and ghrelin genes.

关键词： motilin ghrelin episodic evolution

Factors influencing mercury accumulation in three species of forage fish from Caddo Lake, Texas, USA

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Journal of Environmental Sciences 2010年第8期22卷 1158-1163页

作者： matthew m Chumchal Ray W Drenner david R Cross K david Hambright Department of Biology Texas Christian University 2800 S. University Dr Department of Psychology Texas Christian University 2800 S. University Dr Program in Ecology and Evolutionary Biology Biological Station and Department of Zoology 730 Van Vleet Oval University of Oklahoma

most studies that have examined mercury （Hg） contamination of fish have focused on game species feeding near the top of the food web, while studies that examine forage fish that feed near the base of the food web are rare. We conducted a survey of Hg contamination in three species of forage fish, brook silverside （Labidesthes sicculus）, threadfin shad （Dorosoma petenense） and gizzard shad （Dorosoma cepedianum）, from Caddo Lake, Texas, USA and found species-specific differences in Hg concentrations. We examined total length, age, trophic position （determined using δ15N）, and growth rate of forage fish as factors that could have influenced within-and between-species differences in Hg concentration. Total length and age were the best predictors of within-species differences in Hg concentration. Between-species differences in Hg concentrations were most strongly influenced by trophic position.

关键词： mercury trophic position forage fish

Growth at the microscale:long term thinning effects on patterns and timing of intra-annual stem increment in radiata pine

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Forest Ecosystems 2018年第4期5卷 438-450页

作者： david m.Drew Geoffrey m.Downes Department of Forest and Wood Science Stellenbosch UniversityPrivate Bag X1Matieland 7800South Africa Forest Quality Pty Ltd PO Box 293 HuonvilleTASAustralia.

Background: Stem radial growth in forests is not uniform. Rather, it is characterized by periods of relatively fast or slow growth, or sometimes no growth at all. These fluctuations are generally a function of varying environmental conditions(e.g. water availability) and, importantly, will also be associated with adjustments in proprties in the wood formed. Stand level conditions and forest management, particularly thinning and stand density will, thowever, also have a major influence on patterns of growth variation. We explore how different thinning histories and/or stand densities influence these dynamics of tree growth in the important commercial plantation species Pinus radiata D. ***: Daily stem size change was measured using electronic point dendrometers over two growing seasons on P. radiata trees at two sites, subjected to different thinning regimes. Timing, rates and periodicity of annual growth were calculated from these ***: Greater overall cross-sectional growth in thinned plots was driven mainly by two dynamics. First, the cessation of seasonal growth occurred at least 3 weeks later in the stands in which thinning had taken place. There was no difference between thinned/unthinned stands, however, in the timing of growth onset. Second, within the longer season, trees in thinned plots had more growth days(as much as 20% more) than unthinned plots. The rates of growth on days when growth occurred were not different, however. In this context, it is notable that in trees in the unthinned plots experiencing the most severe competition there were strong "pulses" of growth following drought-breaking rainfall events. Unthinned plots at high stand densities also maintained a smaller(but consistent) zone of dividing cells throughout the season than thinned ***: In Pinus radiata growing under conditions as in our study, conditions late in summer, particularly drought, have an important effect on the timing of cessation of growth. Earl

关键词： monterey pine Dendrometer Intra-annual growth Drought Thinning

Bone–cartilage crosstalk:a conversation for understanding osteoarthritis

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Bone Research 2016年第3期4卷 121-132页

作者： david m Findlay Julia S Kuliwaba Discipline of Orthopaedics and Trauma The University of Adelaide

Although cartilage degradation is the characteristic feature of osteoarthritis （OA）, it is now recognized that the whole joint is involved in the progression of OA. In particular, the interaction （crosstalk） between cartilage and subchondral bone is thought to be a central feature of this process. The interface between articular cartilage and bone of articulating long bones is a unique zone, which comprises articular cartilage, below which is the calcified cartilage sitting on and intercalated into the subchondral bone plate. Below the subchondral plate is the trabecular bone at the end of the respective long bones. In OA, there are well- char described *** destructive tges in the ~cular cartilage, which parallel characteristic changes in the underlying hone, This review examines the evidence that biochemical and biomechanical signaling between these tissue compartments is important in OA disease progression and asks whether such signaling might provide possibilities for therapeutic intervention to halt or slow disease development.

关键词： OA Bone

Ergodicity and Accuracy of Optimal Particle Filters for Bayesian Data Assimilation

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Chinese Annals of mathematics,Series B 2019年第5期40卷 811-842页

作者： david KELLY Andrew m.STUART Courant Institute of mathematical Sciences New York UniversityNew YorkUSAThe Voleon Group2150 Dwight WayBerkeleyCA94704USA Department of Computing and mathematical Sciences California Institute of TechnologyPasadenaCA91125USA.

Data assimilation refers to the methodology of combining dynamical models and observed data with the objective of improving state estimation. most data assimilation algorithms are viewed as approximations of the Bayesian posterior(filtering distribution)on the signal given the observations. Some of these approximations are controlled, such as particle filters which may be refined to produce the true filtering distribution in the large particle number limit, and some are uncontrolled, such as ensemble Kalman filter methods which do not recover the true filtering distribution in the large ensemble limit. Other data assimilation algorithms, such as cycled 3 DVAR methods, may be thought of as controlled estimators of the state, in the small observational noise scenario, but are also uncontrolled in general in relation to the true filtering distribution. For particle filters and ensemble Kalman filters it is of practical importance to understand how and why data assimilation methods can be effective when used with a fixed small number of particles, since for many large-scale applications it is not practical to deploy algorithms close to the large particle limit asymptotic. In this paper, the authors address this question for particle filters and,in particular, study their accuracy(in the small noise limit) and ergodicity(for noisy signal and observation) without appealing to the large particle number limit. The authors first overview the accuracy and minorization properties for the true filtering distribution,working in the setting of conditional Gaussianity for the dynamics-observation model. They then show that these properties are inherited by optimal particle filters for any fixed number of particles, and use the minorization to establish ergodicity of the filters. For completeness we also prove large particle number consistency results for the optimal particle filters, by writing the update equations for the underlying distributions as recursions. In addition to loo

关键词： Particle filters Data assimilation Ergodic theory