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排序方式: 共有5962条查询结果,搜索用时 15 毫秒
61.
Talley TT Harel M Hibbs RE Radic Z Tomizawa M Casida JE Taylor P 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(21):7606-7611
Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 A in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids. 相似文献
62.
Meirav Pevsner-Fischer Vered Morad Michal Cohen-Sfady Liat Rousso-Noori Alexandra Zanin-Zhorov Shmuel Cohen Irun R Cohen Dov Zipori 《Blood》2007,109(4):1422-1432
Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency. 相似文献
63.
Inkjet printing and UV-LED curing of photochromic dyes for functional and smart textile applications
Sina Seipel Junchun Yu Aravin P. Periyasamy Martina Vikov Michal Vik Vincent A. Nierstrasz 《RSC advances》2018,8(50):28395
Health concerns as a result of harmful UV-rays drive the development of UV-sensors of different kinds. In this research, a UV-responsive smart textile is produced by inkjet printing and UV-LED curing of a specifically designed photochromic ink on PET fabric. This paper focuses on tuning and characterizing the colour performance of a photochromic dye embedded in a UV-curable ink resin. The influence of industrial fabrication parameters on the crosslinking density of the UV-resin and hence on the colour kinetics is investigated. A lower crosslinking density of the UV-resin increases the kinetic switching speed of the photochromic dye molecules upon isomerization. By introducing an extended kinetic model, which defines rate constants kcolouration, kdecay and kdecolouration, the colour performance of photochromic textiles can be predicted. Fabrication parameters present a flexible and fast alternative to polymer conjugation to control kinetics of photochromic dyes in a resin. In particular, industrial fabrication parameters during printing and curing of the photochromic ink are used to set the colour yield, colouration/decolouration rates and the durability, which are important characteristics towards the development of a UV-sensor for smart textile applications.Tuned performance of an inkjet-printed and UV-LED cured smart textile UV-sensor based on a photochromic dye using fabrication parameters. 相似文献
64.
Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state.Patient concerns:A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine.Diagnosis:The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia.Outcomes:The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days.Conclusion:The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed. 相似文献
65.
Martina Pecimonova Jan Radvanszky David Smolak Jaroslav Budis Michal Lichvar Diana Kristinova Ivica Rozova Jan Turna Tomas Szemes 《Medicine》2021,100(22)
Rationale:Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene.Patient concerns:We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband''s older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms.Diagnoses:The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband''s genome that absented in any other analyzed family member, suggesting its de novo origin.Interventions and outcomes:The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus.Lessons:We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. 相似文献
66.
Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.KEY WORDS: membrane transporters, molecular imaging, multidrug resistance, near infrared, optical imaging 相似文献
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69.
Effect of Matrix Metalloproteinase Inhibition by Doxycycline on Myocardial Healing and Remodeling after Myocardial Infarction 总被引:2,自引:0,他引:2
Tessone A Feinberg MS Barbash IM Reich R Holbova R Richmann M Mardor Y Leor J 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2005,19(6):383-390
Summary The aim of conducting this study was to assess the clinical relevance of matrix metalloproteinase (MMP) inhibition by doxycycline,
an effective MMP inhibitor, in a rat model of extensive myocardial infarction (MI) and left ventricular (LV) dysfunction.
Rats (n = 22) were subjected to extensive anterior MI. Doxycycline (25 mg SC, daily) or saline (control) injections were started
for nine days thereafter. The effect of doxycycline on MMP activity in the infarcted and remote myocardium was measured by
zymography, in another subgroup (n = 8), nine days after MI. Echocardiography and magnetic resonance imaging (MRI) studies were performed at one and thirty
days after MI to assess LV remodeling and function. After 4 weeks, hearts were fixed, and subjected to morphometric and histological
analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2 activity in both infarcted and remote myocardium.
Serial echocardiography studies showed that doxycycline failed to attenuate scar thinning, LV dilatation and dysfunction.
MRI study showed that doxycycline impaired LV compensatory hypertrophy. Furthermore, compared with control, doxycycline reduced
vessel density (/mm2 ± SEM) in the infarcted myocardium (84 ± 16 vs. 46 ± 9/mm2, respectively; p < 0.05).
Our work suggest that effective MMPs’ inhibition in the infarcted and remote myocardium by doxycycline does not prevent LV
remodeling and dysfunction but impairs angiogenesis and compensatory LV hypertrophy. Our findings caution against aggressive,
non-selective inhibition of MMPs in the early healing phase after MI. 相似文献
70.