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71.
Petya Dimitrova Nina Ivanovska Lyudmila Belenska Viktoriya Milanova Wilhelm Schwaeble Cordula Stover 《Arthritis research & therapy》2012,14(4):1-16
Introduction
Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA).Methods
Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and wild-type (WT) C57BL/6 mice. Symptoms of disease were evaluated daily. The degree of joint damage was assessed histologically and with immunostaining for bone-resorption markers. Phenotypes of cell populations, their receptor expression, and intracellular cytokine production were determined with flow cytometry. Osteoclast differentiation of bone marrow (BM) precursors was evaluated by staining for tartrate-resistant acid phosphatase (TRAP).Results
Properdin-deficient mice developed less severe CAIA than did WT mice. They showed significantly improved clinical scores and downregulated expression of bone-resorption markers in the joints at day 10 of disease. The frequencies of Ly6G+CD11b+ cells were fewer in BM, blood, and synovial fluid (SF) of KO than of WT CAIA mice. The receptor activator of nuclear factor κB ligand (RANKL) was downregulated on arthritic KO neutrophils from BM and the periphery. Decreased C5a amounts in KO SF contributed to lower frequencies of CD5aR+-bearing neutrophils. In blood, surface C5aR was detected on KO Ly6G+ cells as a result of low receptor engagement. Circulating CD4+ T cells had an altered ability to produce interleukin (IL)-17 and interferon (IFN)-γ and to express RANKL. In KO CAIA mice, decreased frequencies of CD4+ T cells in the spleen were related to low CD86 expression on Ly6GhighCD11b+ cells. Arthritic KO T cells spontaneously secreted IFN-γ but not IL-17 and IL-6, and responded to restimulation with less-vigorous cytokine production in comparison to WT cells. Fewer TRAP-positive mature osteoclasts were found in KO BM cell cultures.Conclusions
Our data show that the active involvement of properdin in arthritis is related to an increased proinflammatory cytokine production and RANKL expression on immune cells and to a stimulation of the RANKL-dependent osteoclast differentiation. 相似文献72.
We study a simple traffic model with a non-signalized road intersection. In this model the car arriving from the right has precedence. The vehicle dynamics far from the crossing are governed by the rules introduced by Nagel and Paczuski, which define how drivers behave when braking or accelerating. We measure the average velocity of the ensemble of cars and its flow as a function of the density of cars on the roadway. An additional set of rules is defined to describe the dynamics at the intersection assuming a fraction of drivers that do not obey the rule of precedence. This problem is treated within a game-theory framework, where the drivers that obey the rule are cooperators and those who ignore it are defectors. We study the consequences of these behaviors as a function of the fraction of cooperators and defectors. The results show that cooperation is the best strategy because it maximizes the flow of vehicles and minimizes the number of accidents. A rather paradoxical effect is observed: for any percentage of defectors the number of accidents is larger when the density of cars is low because of the higher average velocity. 相似文献
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74.
Brown A Cornwell T Korniyenko I Solodushko V Bond CT Adelman JP Taylor MS 《American journal of physiology. Cell physiology》2007,292(2):C832-C840
Mechanisms regulating uterine contractility are poorly understood. We hypothesized that a specific isoform of small conductance Ca2+-activated K+ (SK) channel, SK3, promotes feedback regulation of myometrial Ca2+ and hence relaxation of the uterus. To determine the specific functional impact of SK3 channels, we assessed isometric contractions of uterine strips from genetically altered mice (SK3T/T), in which SK3 is overexpressed and can be suppressed by oral administration of doxycycline (SK3T/T+Dox). We found SK3 protein in mouse myometrium, and this expression was substantially higher in SK3T/T mice and lower in SK3T/T+Dox mice compared with wild-type (WT) controls. Sustained contractions elicited by 60 mM KCl were not different among SK3T/T, SK3T/T+Dox, and WT mice. However, the rate of onset and magnitude of spontaneously occurring phasic contractions was muted significantly in isolated uterine strips from SK3T/T mice compared with those from WT mice. These spontaneous contractions were augmented greatly by blockade of SK channels with apamin or by suppression of SK3 expression. Phasic but not tonic contraction in response to oxytocin was depressed in uterine strips from SK3T/T mice, whereas suppression of SK3 channel expression or treatment with apamin promoted the predominance of large coordinated phasic events over tone. Spontaneous contractions and the phasic component of oxytocin contractions were blocked by nifedipine but not by cyclopiazonic acid. Our findings suggest that SK3 channels play an important role in regulating uterine function by limiting influx through L-type Ca2+ channels and disrupting the development of concerted phasic contractile events. uterus; Ca2+-activated K+ channel; doxycycline; mouse 相似文献
75.
Microtubule plus ends are dynamically regulated by a wide variety of proteins for performing diverse cellular functions. Here, we show that the fission yeast Schizosaccharomyces pombe uncharacterized protein mcp1p is a microtubule plus-end tracking protein which depends on the kinesin-8 klp6p for transporting along microtubules towards microtubule plus ends. In the absence of mcp1p, microtubule catastrophe and rescue frequencies decrease, leading to an increased dwell time of microtubule plus ends at cell tips. Thus, these findings suggest that mcp1p may synergize with klp6p at microtubule plus-ends to destabilize microtubules. 相似文献
76.
OsPIN5b modulates rice (Oryza sativa) plant architecture and yield by changing auxin homeostasis,transport and distribution
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Guangwen Lu Viktoriya Coneva José A. Casaretto Shan Ying Kashif Mahmood Fang Liu Eiji Nambara Yong‐Mei Bi Steven J. Rothstein 《The Plant journal : for cell and molecular biology》2015,83(5):913-925
Plant architecture attributes such as tillering, plant height and panicle size are important agronomic traits that determine rice (Oryza sativa) productivity. Here, we report that altered auxin content, transport and distribution affect these traits, and hence rice yield. Overexpression of the auxin efflux carrier‐like gene OsPIN5b causes pleiotropic effects, mainly reducing plant height, leaf and tiller number, shoot and root biomass, seed‐setting rate, panicle length and yield parameters. Conversely, reduced expression of OsPIN5b results in higher tiller number, more vigorous root system, longer panicles and increased yield. We show that OsPIN5b is an endoplasmic reticulum (ER) ‐localized protein that participates in auxin homeostasis, transport and distribution in vivo. This work describes an example of an auxin‐related gene where modulating its expression can simultaneously improve plant architecture and yield potential in rice, and reveals an important effect of hormonal signaling on these traits. 相似文献
77.
Nadezhda E. Yun Alexey V. Seregin David H. Walker Vsevolod L. Popov Aida G. Walker Jeanon N. Smith Milagros Miller Juan C. de la Torre Jennifer K. Smith Viktoriya Borisevich Joseph N. Fair Nadia Wauquier Donald S. Grant Bayon Bockarie Dennis Bente Slobodan Paessler 《Journal of virology》2013,87(19):10908-10911
Lassa fever (LF) is a potentially lethal human disease that is caused by the arenavirus Lassa virus (LASV). Annually, around 300,000 infections with up to 10,000 deaths occur in regions of Lassa fever endemicity in West Africa. Here we demonstrate that mice lacking a functional STAT1 pathway are highly susceptible to infection with LASV and develop lethal disease with pathology similar to that reported in humans. 相似文献
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79.
Robert W. Cross Abhishek N. Prasad Viktoriya Borisevich Courtney Woolsey Krystle N. Agans Daniel J. Deer Natalie S. Dobias Joan B. Geisbert Karla A. Fenton Thomas W. Geisbert 《Cell reports》2021,34(10):108837
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80.
Fan Zheng Tianpeng Li Dong-yan Jin Viktoriya Syrovatkina Kathleen Scheffler Phong T. Tran Chuanhai Fu 《Molecular biology of the cell》2014,25(18):2750-2760
Accurate chromosome segregation requires timely bipolar spindle formation during mitosis. The transforming acidic coiled-coil (TACC) family proteins and the ch-TOG family proteins are key players in bipolar spindle formation. They form a complex to stabilize spindle microtubules, mainly dependent on their localization to the centrosome (the spindle pole body [SPB] in yeast). The molecular mechanism underlying the targeting of the TACC–ch-TOG complex to the centrosome remains unclear. Here we show that the fission yeast Schizosaccharomyces pombe TACC orthologue alp7p is recruited to the SPB by csi1p. The csi1p-interacting region lies within the conserved TACC domain of alp7p, and the carboxyl-terminal domain of csi1p is responsible for interacting with alp7p. Compromised interaction between csi1p and alp7p impairs the localization of alp7p to the SPB during mitosis, thus delaying bipolar spindle formation and leading to anaphase B lagging chromosomes. Hence our study establishes that csi1p serves as a linking molecule tethering spindle-stabilizing factors to the SPB for promoting bipolar spindle assembly. 相似文献