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61.
Gábor Veres Péter Heged?s Enik? Barnucz Raphael Z?ller Stephanie Klein Harald Schmidt Tamás Radovits Sevil Korkmaz Matthias Karck Gábor Szabó 《PloS one》2015,10(4)
Background
Although, ischemia/reperfusion induced vascular dysfunction has been widely described, no comparative study of in vivo- and in vitro-models exist. In this study, we provide a direct comparison between models (A) ischemic storage and in-vitro reoxygenation (B) ischemic storage and in vitro reperfusion (C) ischemic storage and in-vivo reperfusion.Methods and Results
Aortic arches from rats were stored for 2 hours in saline. Arches were then (A) in vitro reoxygenated (B) in vitro incubated in hypochlorite for 30 minutes (C) in vivo reperfused after heterotransplantation (2, 24 hours and 7 days reperfusion). Endothelium-dependent and independent vasorelaxations were assessed in organ bath. DNA strand breaks were assessed by TUNEL-method, mRNA expressions (caspase-3, bax, bcl-2, eNOS) by quantitative real-time PCR, proteins by Western blot analysis and the expression of CD-31 by immunochemistry. Endothelium-dependent maximal relaxation was drastically reduced in the in-vivo models compared to ischemic storage and in-vitro reperfusion group, and no difference showed between ischemic storage and control group. CD31-staining showed significantly lower endothelium surface ratio in-vivo, which correlated with TUNEL-positive ratio. Increased mRNA and protein levels of pro- and anti-apoptotic gens indicated a significantly higher damage in the in-vivo models.Conclusion
Even short-period of ischemia induces severe endothelial damage (in-vivo reperfusion model). In-vitro models of ischemia-reperfusion injury can be limitedly suited for reliable investigations. Time course of endothelial stunning is also described. 相似文献62.
Di Marco GS Rustemeyer P Brand M Koch R Kentrup D Grabner A Greve B Wittkowski W Pavenstädt H Hausberg M Reuter S Lang D 《PloS one》2011,6(9):e24046
Background
Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.Methods
We analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.Results
Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1 – a cytokine responsible for EPC mobilization – is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.Conclusions
We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients. 相似文献63.
64.
Bat species diversity and distribution in a disturbed regime at the Lake Bogoria National Reserve,Kenya 下载免费PDF全文
David B. Wechuli Paul W. Webala Bruce D. Patterson Raphael S. Ochieng 《African Journal of Ecology》2017,55(4):465-476
Human population growth drives intrusion and progressive conversion of natural habitats for agriculture. We evaluated human impacts on bat species diversity and distribution among four vegetation types in and around Lake Bogoria National Reserve between November 2012 and July 2013. Plants were surveyed using the Braun–Blanquet cover/abundance method, whereas bats were sampled using standard mist nets erected on poles at ground level. Floristic similarity analysis revealed three broad vegetation assemblages, namely riverine vegetation, farmland and Acacia woodland/Acacia–Commiphora woodland. Two hundred and 33 bats representing eleven species in eleven genera and seven families were recorded. These were Epomophorus minimus, Rhinolophus landeri, Hipposideros caffer, Cardioderma cor, Lavia frons, Nycteris hispida, Chaerephon pumilus, Mops condylurus, Neoromicia capensis, Scotoecus hirundo and Scotophilus dinganii. Species richness estimators indicated that sampling for bats at ground level was exhaustive. Bat species richness and diversity were highest in the more structurally complex Acacia woodland compared to more homogenous farmlands where we recorded only common and generalist species that often occur in open habitats. The higher bat species richness and diversity in the Acacia woodland as compared to farmland underscore the importance of remnant natural savannah woodlands in the conservation of bats and other elements of biodiversity . 相似文献
65.
66.
Aviva Breuer Christeene G. Haj Manoela V. Foga?a Felipe V. Gomes Nicole Rodrigues Silva Jo?o Francisco Pedrazzi Elaine A. Del Bel Jaime C. Hallak José A. Crippa Antonio W. Zuardi Raphael Mechoulam Francisco S. Guimar?es 《PloS one》2016,11(7)
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4''-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. 相似文献
67.
Mohammed El-Kebir Benjamin J. Raphael Ron Shamir Roded Sharan Simone Zaccaria Meirav Zehavi Ron Zeira 《Algorithms for molecular biology : AMB》2017,12(1):13
Background
Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along a chromosome constitutes the chromosome’s copy-number profile. Understanding how such profiles evolve in cancer can assist in both diagnosis and prognosis.Results
We model the evolution of a tumor by segmental deletions and amplifications, and gauge distance from profile \(\mathbf {a}\) to \(\mathbf {b}\) by the minimum number of events needed to transform \(\mathbf {a}\) into \(\mathbf {b}\). Given two profiles, our first problem aims to find a parental profile that minimizes the sum of distances to its children. Given k profiles, the second, more general problem, seeks a phylogenetic tree, whose k leaves are labeled by the k given profiles and whose internal vertices are labeled by ancestral profiles such that the sum of edge distances is minimum.Conclusions
For the former problem we give a pseudo-polynomial dynamic programming algorithm that is linear in the profile length, and an integer linear program formulation. For the latter problem we show it is NP-hard and give an integer linear program formulation that scales to practical problem instance sizes. We assess the efficiency and quality of our algorithms on simulated instances.Availability
https://github.com/raphael-group/CNT-ILP68.
Raphael Horvath Author Vitae Author Vitae 《Inorganica chimica acta》2011,374(1):10-18
The use of vibrational spectroscopic methods to elucidate the states present in metal complexes of dipyrido[3,2-a:2,3-c]phenazine (dppz) are reviewed. The presence of the close lying b1(ψ) and b1(phz) molecular orbitals leads to a number of close lying intraligand and MLCT excited states. Using resonance Raman spectroscopy the nature of initial photoexcitation may be established as M→b1(ψ). For Ru(II) complexes the lowest excited state is 3MLCT(phz) in nature. However, for [Re(CO)3Cl] complexes the relaxation from the initial excited state may lead to population of a 3MLCT(phen), 3MLCT(phz) state, an state, or an equilibrium between these states. Time-resolved resonance Raman spectroscopy may be used to identify the presence of dppz·- or the state and has also been used to identify features associated with intercalation of dppz complexes with DNA. The Raman methods are less effective at detecting the short time dynamics between these states. However, this may be accomplished using time-resolved infrared spectroscopy in which all three states may be unambiguously determined. The clearest picture of the dynamics in dppz complexes has been achieved by using a combination of time-resolved resonance Raman, time-resolved infrared and DFT calculations for rhenium(I) complexes. 相似文献
69.
Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer 下载免费PDF全文
Yang R Wheeler CM Chen X Uematsu S Takeda K Akira S Pastrana DV Viscidi RP Roden RB 《Journal of virology》2005,79(11):6741-6750
Infection with oncogenic human papillomaviruses (HPVs), typified by HPV type 16 (HPV16), is a necessary cause of cervical cancer. Prophylactic vaccination with HPV16 L1 virus-like particles (VLPs) provides immunity. HPV16 VLPs activate dendritic cells and a potent neutralizing immunoglobulin G (IgG) response, yet many cervical cancer patients fail to generate detectable VLP-specific IgG. Therefore, we examined the role of the innate recognition of HPV16 L1 in VLP-induced immune responses and its evasion during carcinogenesis. Nonconservative mutations within HPV16 L1 have been described in isolates from cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN). We determined the effect of mutations in L1 upon in vitro self-assembly into VLPs and their influence upon the induction of innate and adaptive immune responses in mice. Several nonconservative mutations in HPV16 L1 isolated from high-grade CIN or cervical carcinoma prevent self-assembly of L1 VLPs. Intact VLPs, but not assembly-defective L1, activate dendritic cells to produce proinflammatory factors, such as alpha interferon, that play a critical role in inducing adaptive immunity. Indeed, effective induction of L1-specific IgG1 and IgG2a was dependent upon intact VLP structure. Dendritic cell activation and production of virus-specific neutralizing IgG by VLPs requires MyD88-dependent signaling, although the L1 structure that initiates MyD88-mediated signaling is distinct from the neutralizing epitopes. We conclude that innate recognition of the intact L1 VLP structure via MyD88 is critical in the induction of high-titer neutralizing IgG. Tumor progression is associated with genetic instability and L1 mutants. Selection for assembly-deficient L1 mutations suggests the evasion of MyD88-dependent immune control during cervical carcinogenesis. 相似文献
70.
Acetylcholine receptors in the muscle cell membrane accumulate at the nerve contact area in Xenopus cell cultures. The correlation between spontaneous synaptic potential properties and extent of acetylcholine receptor accumulation was studied. Small and infrequent miniature endplate potentials were measured before acetylcholine receptor accumulation which was observed with fluorescence microscopy using tetramethylrhodamine-conjugated α-bungarotoxin. As acetylcholine receptors accumulate at the nerve contact area, these synaptic potentials become larger and their frequency increases dramatically. In nerve-contacted muscle cells where spontaneous synaptic activity could not be detected, extensive acetylcholine receptor accumulation was not found at sites of nerve contact. Furthermore, muscle cells which exhibited extensive acetylcholine receptor accumulation along the nerve always produced miniature endplate potentials. Thus acetylcholine receptor accumulation and the presence of miniature endplate potentials were strongly correlated. Noncholinergic neurons from dorsal root ganglia did not form functional synaptic contacts with muscle cells nor acetylcholine receptor accumulation along the path of contact. Furthermore, explants from tadpole spinal cord formed functional synaptic contacts with muscle cells but rarely caused AChR localization. These data are discussed in terms of developmental processes during neuromuscular junction formation. 相似文献