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11.
Robert F. Whitcomb Joseph G. Tully David L. Rose Edward B. Stephens Alexis Smith Randolph E. McCoy Michael F. Barile 《Current microbiology》1982,7(5):285-290
Four spiroplasma strains and eleven isolates tentatively identified as acholeplasmas were obtained from fall flowers in Colorado, Nebraska, Illinois, and Maryland. Although the acholeplasma isolates were heterogeneous, all showed antigenic sharing with a group of unnamed organisms (L1 and related strains) isolated in othe studies from flowers in Florida. The W20 and W24 isolates from Nebraska were partially related to the L1 group by DNA-DNA homology and polyacrylamide gel electrophoresis (PAGE) analyses. A Colorado spiroplasma (W13) was identifed as a new strain of group IV complex. Three spiroplasma strains from flowers in Maryland old fields represent a new serovar with closest affinity to subgroup I-4 and to the LB12 and N525 serovars of group I. Widespread occurrence of acholeplasmas on flowers in this study, and on plant surfaces in general, suggests that, like spiroplasmas they probably will be found to reside in arthropods. 相似文献
12.
Alexis D. Phillips Joseph J. Kakkis Patricia Y. Tsao Sheila K. Pierson David C. Fajgenbaum 《Journal of cellular and molecular medicine》2022,26(11):3147
Idiopathic multicentric Castleman disease (iMCD) is a rare and life‐threatening haematologic disorder involving polyclonal lymphoproliferation and organ dysfunction due to excessive cytokine production, including interleukin‐6 (IL‐6). Clinical trial and real‐world data demonstrate that IL‐6 inhibition is effective in 34–50% of patients. mTOR, which functions through mTORC1 and mTORC2, is a recently discovered therapeutic target. The mTOR inhibitor sirolimus, which preferentially inhibits mTORC1, has led to sustained remission in a small cohort of anti‐IL‐6‐refractory iMCD patients with thrombocytopenia, anasarca, fever, renal dysfunction and organomegaly (iMCD‐TAFRO). However, sirolimus has not shown uniform effect, potentially due to its limited mTORC2 inhibition. To investigate mTORC2 activation in iMCD, we quantified the mTORC2 effector protein pNDRG1 by immunohistochemistry of lymph node tissue from six iMCD‐TAFRO and eight iMCD patients who do not meet TAFRO criteria (iMCD‐not‐otherwise‐specified; iMCD‐NOS). mTORC2 activation was increased in all regions of iMCD‐TAFRO lymph nodes and the interfollicular space of iMCD‐NOS compared with control tissue. Immunohistochemistry also revealed increased pNDRG1 expression in iMCD‐TAFRO germinal centres compared with autoimmune lymphoproliferative syndrome (ALPS), an mTOR‐driven, sirolimus‐responsive lymphoproliferative disorder, and comparable staining between iMCD‐NOS and ALPS. These results suggest increased mTORC2 activity in iMCD and that dual mTORC1/mTORC2 inhibitors may be a rational therapeutic approach. 相似文献
13.
Human hemoglobin (Hb) conjugated to benzene tetracarboxylate substituted dextran produces a polymeric Hb (Dex-BTC-Hb) with similar oxygen affinity to that of red blood cells (P(50)=28-29 mm Hg). Under physiological conditions, the oxygen affinity (P(50)) of Dex-BTC-Hb is 26 mm Hg, while that of native purified human HbA(0) is 14 mm Hg, but it exhibits a slight reduction in cooperativity (n(50)), Bohr effect, and lacks sensitivity to inositol hexaphosphate (IHP), when compared to HbA(0). Oxygen-binding kinetics, measured by rapid mixing stopped-flow method showed comparable oxygen dissociation and association rates for both HbA(0) and Dex-BTC-Hb. The rate constant for NO-mediated oxidation of the oxy form of Dex-BTC-Hb, which is governed by NO entry to the heme pocket, was reduced to half of the value obtained for HbA(0). Moreover, Dex-BTC-Hb is only slightly more sensitive to oxidative reactions than HbA(0), as shown by about 2-fold increase in autoxidation, and slightly higher H(2)O(2) reaction and heme degradation rates. Dextran-BTC-based modification of Hb produced an oxygen-carrying compound with increased oxygen release rates, decreased oxygen affinity and reduced nitric oxide scavenging, desirable properties for a viable blood substitute. However, the reduction in the allosteric function of this protein and the lack of apparent quaternary T-->R transition may hinder its physiological role as an oxygen transporter. 相似文献
14.
Anion channels and transporters in plant cell membranes 总被引:2,自引:0,他引:2
de Angeli A Thomine S Frachisse JM Ephritikhine G Gambale F Barbier-Brygoo H 《FEBS letters》2007,581(12):2367-2374
15.
Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system 总被引:3,自引:0,他引:3
Tang GP Guo HY Alexis F Wang X Zeng S Lim TM Ding J Yang YY Wang S 《The journal of gene medicine》2006,8(6):736-744
BACKGROUND: Polyethylenimines (PEIs) with high molecular weights are effective nonviral gene delivery vectors. However, the in vivo use of these PEIs can be hampered by their cellular toxicity. In the present study we developed and tested a new PEI polymer synthesized by linking less toxic, low molecular weight (MW) PEIs with a commonly used, biocompatible drug carrier, beta-cyclodextrin (CyD). METHODS AND RESULTS: The terminal CyD hydroxyl groups were activated by 1,1'-carbonyldiimidazole. Each activated CyD then linked two branched PEI molecules with MW of 600 Da to form a CyD-containing polymer with MW of 61 kDa, in which CyD served as a part of the backbone. The PEI-CyD polymer developed was soluble in water and biodegradable. In cell viability assays with sensitive neurons, the polymer performed similarly to low-MW PEIs and displayed much lower cellular cytotoxicity compared to PEI 25 kDa. The gene delivery efficiency of the polymer was comparable to, and at higher polymer/DNA ratios even higher than, that offered by PEI 25 kDa in neural cells. Attractively, intrathecal injection of plasmid DNA complexed by the polymer into the rat spinal cord provided levels of gene expression close to that offered by PEI 25 kDa. CONCLUSIONS: The polymer reported in the current study displayed improved biocompatibility over non-degradable PEI 25 kDa and mediated gene transfection in cultured neurons and in the central nervous system effectively. The new polymer would be worth exploring further as an in vivo delivery system of therapeutic genetic materials for gene therapy of neurological disorders. 相似文献
16.
17.
Acosta-Rivero N Rodriguez A Musacchio A Falcón V Suarez VM Martinez G Guerra I Paz-Lago D Morera Y de la Rosa MC Morales-Grillo J Dueñas-Carrera S 《Biochemical and biophysical research communications》2004,325(1):68-74
Different variants of hepatitis C virus core protein (HCcAg) have proved to self-assemble in vitro into virus-like particles (VLPs). However, difficulties in obtaining purified mature HCcAg have limited these studies. In this study, a high degree of monomeric HCcAg purification was accomplished using chromatographic procedures under denaturing conditions. Size exclusion chromatography and sucrose density gradient centrifugation of renatured HCcAg (in the absence of structured RNA) under reducing conditions suggested that it assembled into empty capsids. The electron microscopy analysis of renatured HCcAg showed the presence of spherical VLPs with irregular shapes and an average diameter of 35nm. Data indicated that HCcAg monomers assembled in vitro into VLPs in the absence of structured RNA, suggesting that recombinant HCcAg used in this work contains all the information necessary for the assembly process. However, they also suggest that some cellular factors might be required for the proper in vitro assembly of capsids. 相似文献
18.
19.
Cilia‐localized LKB1 regulates chemokine signaling,macrophage recruitment,and tissue homeostasis in the kidney
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Kamile Lukas Abhijeet P Todkar Manuel Knoll Toma A Yakulov Alexis Hofherr Oliver Kretz Martin Helmstädter Wilfried Reichardt Simone Braeg Tom Aschman Annette Merkle Dietmar Pfeifer Verónica I Dumit Marie‐Claire Gubler Roland Nitschke Tobias B Huber Fabiola Terzi Jörn Dengjel Florian Grahammer Michael Köttgen Hauke Busch Melanie Boerries Gerd Walz Antigoni Triantafyllopoulou E Wolfgang Kuehn 《The EMBO journal》2018,37(15)
Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy‐related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell‐autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis. 相似文献
20.
Beno?te Méry Jean-Baptiste Guy Sophie Espenel Anne-Sophie Wozny Stéphanie Simonet Alexis Vallard Gersende Alphonse Dominique Ardail Claire Rodriguez-Lafrasse Nicolas Magné 《World journal of stem cells》2016,8(1):13-21
Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities. 相似文献