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201.
Rabbit platelet membranes, preincubated with 3H-labeled platelet activating factor ([3H]PAF), were solubilized with 2% digitonin. Sedimentation of the detergent extract in a sucrose density gradient revealed a major labeled component with a sedimentation coefficient (s20,omega) of 10.5 S, which was substantially diminished when an excess of unlabeled PAF or L-652,731, (trans-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran), (PAF antagonist) was present in the preincubation mixture, suggesting that the 10.5 S component is a specific receptor-bound [3H]PAF complex. Gel filtration of the [3H]PAF-receptor complex on Sephacryl S-300 revealed a single radiolabeled fraction with an apparent Stokes' radius of 4.9 nm. The apparent molecular weight and the frictional ratio of the agonist-receptor complex were computed to be 220,000 and 1.13, respectively. Dissociation of [3H]PAF from the radioligand-receptor complex was facilitated by Na+ and Li+, whereas K+ and Cs+ were ineffective. The guanine nucleotide, GTP, was also found to promote the dissociation in a manner that is additive with the effect of Na+, suggestive of the coupling of a guanine nucleotide binding protein to the solubilized PAF-receptor complex. 相似文献
202.
Summary Immobilized cell technology frequently relies on the entrapment of the biomass in a gel particle, and it is generally observed
that mass transfer limitations within the gel particle lead to nonuniform cell distribution. This note addresses the consequence
of maintaining a very high cell mass density within a biopolymer particle. We illustrate that conventional effectiveness factor
calculations can be used to determine particle sizes which would avoid nonuniform cell growth. The analysis is based on simple
Monod kinetics. Special attention is given to near zero order kinetic systems in which the effectiveness factor remains high
although the limiting nutrient may be depleted near the center of the particle.
Mina Dalili is at the Department of Chemical Engineering, North Carolina State University 相似文献
203.
Lalu Muhammad Irham Wirawan Adikusuma Dyah Aryani Perwitasari Haafizah Dania Rita Maliza Imaniar Noor Faridah Ichtiarini Nurullita Santri Yohane Vincent Abero Phiri Rocky Cheung 《Biochemistry and Biophysics Reports》2022
BackgroundOne of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB.MethodThe genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)).ResultsA total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores.ConclusionThrough the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB. 相似文献
204.
205.
Coxsackievirus B3 (CVB3) is a positive, single-stranded RNA virus. The secondary structure of the 3' untranslated region (3'UTR) of CVB3 RNA consists of three stem-loops and is followed by a poly(A) tail sequence. These stem-loop structures have been suggested to participate in the regulation of viral replication through interaction with cellular proteins that are yet to be identified. In this study, by competitive UV cross-linking using mutated 3'UTR probes we have demonstrated that the poly(A) tail is essential for promoting HeLa cell protein interactions with the 3'UTR because deletion of this sequence abolished most of the protein interactions. Unexpectedly, mutations that disrupted the tertiary loop-loop interactions without affecting the stem-loops did not apparently affect these protein interactions, indicating that secondary structure rather than the high-order structure may play a major role in recruiting these RNA binding proteins. Among the observed 3'UTR RNA binding proteins, we have confirmed a 52 kDa protein as the human La autoantigen by using purified recombinant protein and a polyclonal La antibody. This protein can interact with both the 3' and 5'UTRs independently of the poly(A) tail. Further analysis by two-stage UV cross-linking, we found that the 3' and 5'UTR sequences may share the same binding site on the La protein. 相似文献
206.
James A. Daniel Ngoc Chau Mohammed K. Abdel‐Hamid Lingbo Hu Lisa von Kleist Ainslie Whiting Sai Krishnan Peter Maamary Shannon R. Joseph Fiona Simpson Volker Haucke Adam McCluskey Phillip J. Robinson 《Traffic (Copenhagen, Denmark)》2015,16(6):635-654
Chlorpromazine is a phenothiazine‐derived antipsychotic drug (APD) that inhibits clathrin‐mediated endocytosis (CME) in cells by an unknown mechanism. We examined whether its action and that of other APDs might be mediated by the GTPase activity of dynamin. Eight of eight phenothiazine‐derived APDs inhibited dynamin I (dynI) in the 2–12 µm range, the most potent being trifluoperazine (IC50 2.6 ± 0.7 µm ). They also inhibited dynamin II (dynII) at similar concentrations. Typical and atypical APDs not based on the phenothiazine scaffold were 8‐ to 10‐fold less potent (haloperidol and clozapine) or were inactive (droperidol, olanzapine and risperidone). Kinetic analysis showed that phenothiazine‐derived APDs were lipid competitive, while haloperidol was uncompetitive with lipid. Accordingly, phenothiazine‐derived APDs inhibited dynI GTPase activity stimulated by lipids but not by various SH3 domains. All dynamin‐active APDs also inhibited transferrin (Tfn) CME in cells at related potencies. Structure–activity relationships (SAR) revealed dynamin inhibition to be conferred by a substituent group containing a terminal tertiary amino group at the N2 position. Chlorpromazine was previously proposed to target AP‐2 recruitment in the formation of clathrin‐coated vesicles (CCV). However, neither chlorpromazine nor thioridazine affected AP‐2 interaction with amphiphysin or clathrin. Super‐resolution microscopy revealed that chlorpromazine blocks neither clathrin recruitment by AP‐2, nor AP‐2 recruitment, showing that CME inhibition occurs downstream of CCV formation. Overall, potent dynamin inhibition is a shared characteristic of phenothiazine‐derived APDs, but not other typical or atypical APDs, and the data indicate that dynamin is their likely in‐cell target in endocytosis. 相似文献
207.
The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases 总被引:1,自引:0,他引:1
Maia A. Rabaa Ngo Tri Tue Tran My Phuc Juan Carrique-Mas Karen Saylors Matthew Cotten Juliet E. Bryant Ho Dang Trung Nghia Nguyen Van Cuong Hong Anh Pham Alessandra Berto Voong Vinh Phat Tran Thi Ngoc Dung Long Hoang Bao Ngo Thi Hoa Heiman Wertheim Behzad Nadjm Corina Monagin H. Rogier van Doorn Motiur Rahman My Phan Vu Tra James I. Campbell Maciej F. Boni Pham Thi Thanh Tam Lia van der Hoek Peter Simmonds Andrew Rambaut Tran Khanh Toan Nguyen Van Vinh Chau Tran Tinh Hien Nathan Wolfe Jeremy J. Farrar Guy Thwaites Paul Kellam Mark E. J. Woolhouse Stephen Baker 《EcoHealth》2015,12(4):726-735
208.
H Wadsworth PA Jones WF Chau C Durrant V Morisson-Iveson J Passmore D O'Shea D Wynn I Khan A Black M Avory W Trigg 《Bioorganic & medicinal chemistry letters》2012,22(18):5795-5800
A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents. 相似文献
209.
SUMO (small ubiquitin-related modifier)-specific proteases catalyse the maturation and de-conjugation processes of the sumoylation pathway and modulate various cellular responses including nuclear metabolism and cell cycle progression. The active-site cysteine residue is conserved among all known SUMO-specific proteases and is not substitutable by serine in the hydrolysis reactions demonstrated previously in yeast. We report here that the catalytic domain of human protease SENP1 (SUMO-specific protease 1) mutant SENP1C(C603S) carrying a mutation of cysteine to serine at the active site is inactive in maturation and de-conjugation reactions. To further understand the hydrolytic mechanism catalysed by SENP1, we have determined, at 2.8 A resolution (1 A = 0.1 nm), the X-ray structure of SENP1C(C603S)-SUMO-1 complex. A comparison of the structure of SENP2-SUMO-1 suggests strongly that SUMO-specific proteases require a self-conformational change prior to cleavage of peptide or isopeptide bond in the maturation and de-conjugation processes respectively. Moreover, analysis of the interface of SENP1 and SUMO-1 has led to the identification of four unique amino acids in SENP1 that facilitate the binding of SUMO-1. By means of an in vitro assay, we further demonstrate a novel function of SENP1 in hydrolysing the thioester linkage in E1-SUMO and E2-SUMO complexes. The results disclose a new mechanism of regulation of the sumoylation pathway by the SUMO-specific proteases. 相似文献
210.