Search
Filter Results
Search Results
Sort by
- Book[edited by] Jane R. Madell, PhD, CCC-A/SLP, ABA, LSLS Cert AVT, Director, ... Show More Pediatric Audiology Consulting, New York, New York, Carol Flexer, PhD, CCC-A, LSLS Cert. AVT, Distinguished Professor Emeritus, Audiology, School of Speech-Language Pathology and Audiology, the University of Akron, Akron, Ohio.Summary: "Pediatric Audiology Casebook bridges the gap between content knowledge and clinical application in an accessible manner that will enable readers to put learned theory into active practice by engaging them in problem-based learning. This compendium of key cases is an excellent choice for the classroom, covering everything from basic and complex diagnostic cases, to hearing aid technology, vestibular issues, and the management of auditory development. Each case is consistently organized, beginning with the patient's clinical history and audiologic testing. The authors then pose a series of evaluative questions to the reader, followed by carefully considered, thought-provoking answers designed to foster understanding. Cases close with a discussion of the definitive diagnosis, recommended treatment options, and the final outcome"--Provided by publisherDigital Access Thieme MedOne ComSci ©2011
- ArticleWasifuddin M, Ilerhunmwuwa N, Uche I, Aiwuyo HO, Hakobyan N, Sedeta E, Perry JC, Torere BE, Abowali HA, Mararenko L.Cureus. 2023 Jan;15(1):e34354.Endometrial cancer is the most common cancer of the female genital tract. It can rarely metastasize to the pleura and present as a malignant pleural effusion. Here we present the case of a 61-year-old female with two primary malignancies, breast and endometrium, who presented to us with shortness of breath. Imaging was suggestive of a malignant pleural effusion. Diagnostic and therapeutic thoracentesis were performed that were initially suggestive of a breast source. However, final pleural fluid studies showed endometrial serous carcinoma as the source of the effusion. The patient received pembrolizumab and lenvatinib treatment and continues to be followed up in our clinic.
- ArticleLalu MM, Foster M, Presseau J, Dowlatshahi D, Castillo G, Cardenas A, Tam W, Zlepnig J, Timpson D, Dong YY, Juneau P, Fergusson DA.BMJ Open. 2020 03 19;10(3):e034354.OBJECTIVES: Early phase cell therapy trials face many barriers to successful, timely completion. To optimise the conduct of a planned clinical trial of mesenchymal stem cell (MSC) therapy for chronic stroke, we sought patient and physician views on possible barriers and enablers that may influence their participation.
DESIGN: Semistructured interview study.
SETTING: Patients were recruited from three rehabilitation centres in Ontario, Canada; physicians were recruited from across Canada through snowball sampling.
PARTICIPANTS: Thirteen chronic stroke patients (patients who had experienced a stroke at least 3 months prior; 10 male, 3 female) and 15 physicians (stroke physiatrists; 9 male, 6 female) participated in our interview study. Data adequacy was reached after 13 patient interviews and 13 physician interviews.
METHODS: Interview guides and directed content analysis were based on the Theoretical Domains Framework (TDF). Interviews were coded, and relevant themes were identified.
RESULTS: Most patients were optimistic about participating in an MSC therapy clinical trial, and many expressed interest in participating, even if it was a randomised controlled trial with the possibility of being allocated to a placebo group. However, the method of administration of cells (intravascular preferred to intracerebral) and goal of the trial (efficacy preferred to safety) may influence their intention to participate. All physicians expressed interest in screening for the trial, though many stated they were less motivated to contribute to a safety trial. Physicians also identified several time-related barriers and the need for resources to ensure feasibility.
CONCLUSIONS: This novel application of the TDF helped identify key potential barriers and enablers prior to conducting a clinical trial of MSC therapy for stroke. This will be used to refine the design and conduct of our trial. A similar approach may be adopted by other investigators considering early phase cell therapy trials. - ArticleCheng J, Ni J, Zhang Q, Fan Y.Medicine (Baltimore). 2023 Jul 14;102(28):e34354.Global coronavirus disease 2019 pandemic leads to the soaring demand for medical statistical applications, bringing a great challenge to medical education at universities worldwide. The purpose of our study is to investigate medical students and teachers attitudes and demands on statistical software education. A multi-city cross-sectional study was conducted in 2021 at medical universities in eastern China. Students and teachers were surveyed through online electronic questionnaires. We collected information on each participant attitudes and demands on medical statistical software usage experience. A total of 895 responses were collected using a validated questionnaire. Most students showed great interest in learning medical statistical software (undergraduates 91.9% vs post-graduates 97.8%, P < .01), thought that statistical software was important (undergraduates 99.2% vs post-graduates 94.7%, P < .01), highly relied on using the SPSS (undergraduates 52.9 % vs post-graduates 77.6%, P < .01) and R package, and felt difficulty in learning statistical software (undergraduates 82.7% vs post-graduates 98.4%, P < .01). Among teachers, the most commonly used statistical software was SPSS (91.2%), followed by the R package. Notably, very few students and teachers thought "Statistical software met needs" (from 21.8% of undergraduates to 8.8% of teachers). There were 75.4% of post-graduates and 96.5% of teachers who thought it was necessary for a university to offer an advanced statistical software curriculum such as the R package in the preferred teaching format of offline class as well as the combination of theory and software practice teaching. This study for the first time demonstrated that most medical undergraduates, post-graduates, and teachers in Anhui Province of eastern China were not satisfied with statistical software usage experience, calling for prompt adjustments to statistical software education in medical universities.
- ArticleXu N, Lu X, Kavi H, Emelyanov AV, Bernardo TJ, Vershilova E, Skoultchi AI, Fyodorov DV.Sci Rep. 2016 Sep 30;6:34354.Metazoan linker histones are essential for development and play crucial roles in organization of chromatin, modification of epigenetic states and regulation of genetic activity. Vertebrates express multiple linker histone H1 isoforms, which may function redundantly. In contrast, H1 isoforms are not present in Dipterans, including D. melanogaster, except for an embryo-specific, distantly related dBigH1. Here we show that Drosophila BEN domain protein Elba2, which is expressed in early embryos and was hypothesized to have insulator-specific functions, can compensate for the loss of H1 in vivo. Although the Elba2 gene is not essential, its mutation causes a disruption of normal internucleosomal spacing of chromatin and reduced nuclear compaction in syncytial embryos. Elba2 protein is distributed ubiquitously in polytene chromosomes and strongly colocalizes with H1. In H1-depleted animals, ectopic expression of Elba2 rescues the increased lethality and ameliorates abnormalities of chromosome architecture and heterochromatin functions. We also demonstrate that ectopic expression of BigH1 similarly complements the deficiency of H1 protein. Thus, in organisms that do not express redundant H1 isoforms, the structural and biological functions performed by canonical linker histones in later development, may be shared in early embryos by weakly homologous proteins, such as BigH1, or even unrelated, non-homologous proteins, such as Elba2.
- ArticleFigueiredo AC, Clement CC, Zakia S, Gingold J, Philipp M, Pereira PJ.PLoS One. 2012;7(3):e34354.The tremendous social and economic impact of thrombotic disorders, together with the considerable risks associated to the currently available therapies, prompt for the development of more efficient and safer anticoagulants. Novel peptide-based thrombin inhibitors were identified using in silico structure-based design and further validated in vitro. The best candidate compounds contained both L- and D-amino acids, with the general sequence D-Phe(P3)-Pro(P2)-D-Arg(P1)-P1'-CONH₂. The P1' position was scanned with L- and D-isomers of natural or unnatural amino acids, covering the major chemical classes. The most potent non-covalent and proteolysis-resistant inhibitors contain small hydrophobic or polar amino acids (Gly, Ala, Ser, Cys, Thr) at the P1' position. The lead tetrapeptide, D-Phe-Pro-D-Arg-D-Thr-CONH₂, competitively inhibits α-thrombin's cleavage of the S2238 chromogenic substrate with a K(i) of 0.92 µM. In order to understand the molecular details of their inhibitory action, the three-dimensional structure of three peptides (with P1' L-isoleucine (fPrI), L-cysteine (fPrC) or D-threonine (fPrt)) in complex with human α-thrombin were determined by X-ray crystallography. All the inhibitors bind in a substrate-like orientation to the active site of the enzyme. The contacts established between the D-Arg residue in position P1 and thrombin are similar to those observed for the L-isomer in other substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57-Ser195 hydrogen bond, while the combination of a P1 D-Arg and a bulkier P1' residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the scissile bond by the catalytic serine. The experimental models explain the observed relative potency of the inhibitors, as well as their stability to proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a novel pharmacophore platform for developing antithrombotic agents by exploring the conformational constrains imposed by the D-stereochemistry of the residues at positions P1 and P1'.
- ArticleWang L, Qin Y, Wang Y, Zhou Y, Liu B, Bai M, Tong X, Fang R, Huang X.RSC Adv. 2021 Oct 18;11(54):34343-34354.The inhibition mechanism of two homoisoflavonoids from Ophiopogon japonicus including methylophiopogonanone A (MO-A) and methylophiopogonanone B (MO-B) on tyrosinase (Tyr) was studied by multiple spectroscopic techniques and molecular docking. The results showed that the two homoisoflavonoids both inhibited Tyr activity via a reversible mixed-inhibition, with a half inhibitory concentration (IC50) of (10.87 ± 0.25) × 10-5 and (18.76 ± 0.14) × 10-5 mol L-1, respectively. The fluorescence quenching and secondary structure change of Tyr caused by MO-A and B are mainly driven by hydrophobic interaction and hydrogen bonding. Molecular docking analysis indicated that phenylmalandioxin in MO-A and methoxy in MO-B could coordinate with a Cu ion in the active center of Tyr, and interacted with amino acid Glu322 to form hydrogen bonding, occupying the catalytic center to block the entry of the substrate and consequently inhibit Tyr activity. This study may provide new perspectives on the inhibition mechanism of MO-A and MO-B on Tyr and serve a scientific basis for screening effective Tyr inhibitors.
- ArticleMahakal S, Pathan HM, Prasad M, Rondiya S, Patole SP, Jadkar SR.ACS Omega. 2023 Sep 26;8(38):34354-34363.This paper presents a comparative study of the toxicity of pristine-ZnO and l-histidine-incorporated ZnO toward Escherichia coli (E. coli) as a Gram-negative model organism. Pristine-ZnO and l-histidine-incorporated ZnO with different l-histidine concentrations were synthesized using an open aqueous solution bath technique. XRD studies revealed the formation of polycrystalline wurtzite ZnO. The average crystallite size of the synthesized l-histidine-incorporated ZnO decreased as the concentration of l-histidine increased. The FTIR spectra showed the presence of Zn-O, CO2-/CO3-, and C-N (only in l-histidine-incorporated ZnO samples) and -OH bond vibration signals in all samples. The chemical purity of all the samples was ensured using XPS analysis. The microbial activity of these samples was investigated using E. coli. The solution with 100 μg/mL ZnO in sterile distilled water showed up to 94% growth inhibition of E. coli, establishing antibacterial activity. However, l-histidine incorporated in ZnO showed reduced antibacterial activity with the increase of the concentration of l-histidine in ZnO. Furthermore, flow cytometry studies during the interaction of ZnO and E. coli confirmed the generation of reactive oxygen species (ROS), validating its antibacterial activity. The interaction of l-histidine-incorporated ZnO and E. coli showed declining ROS with the increase in the l-histidine concentration, indicating a ZnO toxicity reduction.
- ArticlePayvandi L, Parsons C, Bourgeois FC, Hron JD.JMIR Form Res. 2022 Apr 19;6(4):e34354.BACKGROUND: Patients with limited English proficiency (LEP) are at a higher risk of poor health outcomes and are less likely to use telehealth than English-speaking patients. To date, there is no formal evaluation of inpatient (IP) telehealth user experience of patients and their families by language preference during visits with their clinicians.
OBJECTIVE: This study aims to compare the experiences of English- and Spanish-speaking patients and their families using IP telehealth, as well as to evaluate the experience of Spanish interpreters providing services through IP telehealth.
METHODS: We prospectively administered a survey to English- and Spanish-speaking patients and their families who used IP telehealth from October 1, 2020, to March 31, 2021. We performed semistructured phone interviews of hospital-based Spanish interpreters who provided services through IP telehealth.
RESULTS: A total of 661 surveys were administered, with completion rates of 18% (112/621) in English and 62% (25/40) in Spanish. On a 10-point scale, the overall satisfaction of Spanish speakers (median 10, IQR 10-10) was higher than that of English speakers (median 9, IQR 8-10; P=.001). Both English- and Spanish-speaking patients used IP telehealth for visits with their primary IP care team, subspecialty consultants, and other clinicians. Hospital tablets were used more often than personal devices, and only English-speaking patients used personal laptops. Patients and their families encountered challenges with log-in, team coordination with multiple users, and equipment availability. Interpreters encountered challenges with audio and video quality, communication, safety, and Wi-Fi access.
CONCLUSIONS: Both English- and Spanish-speaking patients reported high satisfaction using IP telehealth across multiple disciplines despite the workflow challenges identified by interpreters. Significant investment is needed to provide robust infrastructure to support use by all patients, especially the integration of multiple users to provide interpreter services for patients with LEP. - ArticleOsyanin VA, Osipov DV, Semenova IA, Korzhenko KS, Lukashenko AV, Demidov OP, Klimochkin YN.RSC Adv. 2020 Sep 16;10(57):34344-34354.Various substituted polycyclic pyrano[2,3-b]pyrans were synthesized via the condensation of 4H-chromene-3-carbaldehydes and their areno-condensed analogues with hetero- and carbocyclic 1,3-dicarbonyl compounds in acetic acid. Ammonium acetate was used as a green catalyst for the reaction. The process also involves the subsequent Knoevenagel condensation and 6π-electrocyclization of the 1-oxatriene intermediates formed. Fused pyridines were isolated as the products of the conjugated addition of ammonia to 1-oxatriene intermediates while using carbocyclic 1,3-dicarbonyl compounds and increasing the reaction time, indicating the reversibility of the electrocyclization stage. The calculated values of the Gibbs free energies and reaction rate constants for the 1-oxatriene - 2H-pyran equilibrium also testified to the irreversibility of pyrano[2,3-b]pyran formation in the case of using of heterocyclic 1,3-dicarbonyl compounds.
- ArticleGao M, Xu Y, Chang X, Song Z.Environ Sci Pollut Res Int. 2021 Jul;28(26):34344-34354.A detailed study of nanomaterials has revealed their broad application prospects. However, the presence of carbon nanotubes (CNTs) in the environment has been increasing and has aroused concerns regarding their toxicity to crops when combined with heavy metals. In the present study, the effects of Cd on the photosynthetic capacity and antioxidant activity of wheat seedlings in the presence of single-walled CNTs (SW) and multi-walled CNTs (MW) were investigated. Our results indicated that SW (5-40 mg L-1) and MW (10-40 mg L-1) significantly increased the oxidative stress response of wheat seedlings to Cd. Compared with Cd alone, CNTs combined with Cd decreased net photosynthetic rate, stomatal conductance, transpiration rate, primary maximum photochemical efficiency of photosystem II, actual quantum yield, photosynthetic electron transport rate, root canal protein, and ribulose-1,5-bisphosphate carboxylase/oxygenase content. Moreover, combined treatments increased the content of superoxide anion, superoxide dismutase, guaiacol peroxidase, cytochrome, and malondialdehyde in wheat seedlings. Moreover, membrane lipid peroxidation was aggravated, causing serious damage to the wheat membrane system. In addition, the toxicity of the SW treatment and the combined treatment with SW and Cd was higher than that of the MW treatment.
- ArticleNieves LM, Dong YC, Rosario-Berríos DN, Mossburg K, Hsu JC, Cramer GM, Busch TM, Maidment ADA, Cormode DP.ACS Appl Mater Interfaces. 2022 Aug 03;14(30):34354-34364.The use of nanoparticles in the biomedical field has gained much attention due to their applications in biomedical imaging, drug delivery, and therapeutics. Silver telluride nanoparticles (Ag2Te NPs) have been recently shown to be highly effective computed tomography (CT) and dual-energy mammography contrast agents with good stability and biocompatibility, as well as to have potential for many other biomedical purposes. Despite their numerous advantageous properties for diagnosis and treatment of disease, the clinical translation of Ag2Te NPs is dependent on achieving high levels of excretion, a limitation for many nanoparticle types. In this work, we have synthesized and characterized a library of Ag2Te NPs and identified conditions that led to 3 nm core size and were renally excretable. We found that these nanoparticles have good biocompatibility, strong X-ray contrast generation, and rapid renal clearance. Our CT data suggest that renal elimination of nanoparticles occurred within 2 h of administration. Moreover, biodistribution data indicate that 93% of the injected dose (%ID) has been excreted from the main organs in 24 h, 95% ID in 7 days, and 97% ID in 28 days with no signs of acute toxicity in the tissues studied under histological analysis. To our knowledge, this renal clearance is the best reported for Ag2Te NP, while being comparable to the highest renal clearance reported for any type of nanoparticle. Together, the results herein presented suggest the use of GSH-Ag2Te NPs as an X-ray contrast agent with the potential to be clinically translated in the future.
- ArticleWang J, Li M, Shen W, Su W, He R.ACS Appl Mater Interfaces. 2019 Sep 18;11(37):34348-34354.Having suffered from intrinsic structural lability, perovskite quantum dots (PQDs) are extremely unstable under high-temperature and moisture conditions, which have greatly limited their applications. In this work, we propose a novel method to synthesize ultrastable carbon quantum dots (CQDs)-doped methylamine (MA) lead bromide PQDs with SiO2 encapsulation (CQDs-MAPbBr3@SiO2). The kernel CQDs-MAPbBr3 is formed by the interaction of carboxyl-rich CQDs with MAPbBr3 via H-bond, which greatly improves the thermal stability of CQDs-MAPbBr3. Furthermore, highly compact SiO2 encapsulates the proposed CQDs-MAPbBr3 via a facile in situ growth strategy, which effectively enhances the water resistance and air stability of CQDs-MAPbBr3@SiO2. As a result, the proposed nanomaterial shows extremely high water stability in aqueous solution for over 9 months and ideal thermal stability with strong fluorescence (FL) emission after 150 °C annealing. Based on the superior stability and ultrahigh FL efficiency of this proposed nanomaterial, a primary sensing method for ion (Ag+ and Zn2+) FL detection has been developed and the mechanism of PQDs-based ion determination has also been discussed, thus exhibiting the potential applications of CQDs-MAPbBr3@SiO2 in the area of FL assay and environment monitoring.
- ArticleZhang G, Zhao P, Xu Y, Yang Z, Cheng H, Zhang Y.ACS Appl Mater Interfaces. 2018 Oct 10;10(40):34340-34354.In order to investigate the influence of support structure properties on CO2 capture performances of solid amine adsorbents, a novel three-dimensional disordered porous silica (3dd) with hierarchical pore networks was developed and then compared to other three materials as adsorbent support, namely, hierarchical porous silica (HPS), MCM-41, and SBA-15. They were all functionalized with tetraethylenepentaamine (TEPA) to prepare CO2 adsorbents. The adsorbents' ability to capture CO2 was examined on a fixed-bed reactor. When these supports had 60 wt% TEPA loading, the amounts of CO2 captured followed the order 3dd > HPS > SBA-15 > MCM-41 at 75 °C; the adsorption capacities were 5.09, 4.9, 4.58, and 2.49 mmol/g, respectively. The results indicate that a larger pore volume can promote the dispersion of amine species to expose more active sites for CO2 capture. The larger pore size can decrease the CO2 diffusion resistance. High surface area is not an important factor in determining capture performance. In addition, compared with conventional single-size mesopores, the hierarchical pore networks can disperse the TEPA species in different levels of the channel to limit undesired loss/aggregation of impregnated TEPA species. Thus, the 3dd support exhibits the best stability and highest regeneration conversion compared to the other three supports. This work demonstrates that the rational design of adsorbent support systems can effectively relieve the trade-off between amine loading and diffusion resistance. One method to surmount this trade-off is to utilize an adsorbent platform with hierarchical pore networks. Thus, this work may provide a feasible strategy for the design of CO2 solid amine adsorbents with high capture amount and amine utilization efficiency.
- BookJane R. Madell, PhD, FAAA, CCC-A/SLP, LSLS Cert AVT, Director Pediatric Audiology Consulting, ... Show More New York, New York, Carol Flexer, PhD, FAAA, CCC-A, LSLS Cert AVT, Consultant in Pediatric Audiology Distinguished Professor Emeritus, Audiology School of Speech-Language Pathology and Audiology The University of Akron, Akron, Ohio, Jace Wolfe, PhD, CCC-A, Director of Audiology Hearts for Hearing Foundation Adjunct Assistant Professor Department of Audiology University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, Erin C. Schafer, PhD, FAAA, CCC-A, Professor Department of Audiology and Speech-Language Pathology College of Health and Public Service University of North Texas, Denton, Texas.Summary: "Leverages real-life cases to foster in-depth understanding of pediatric audiology Pediatric Audiology Casebook, Second Edition is fully updated with more than 60 new cases presented in four sections, covering all facets of the diagnosis and management of hearing disorders in children. Renowned experts Jane R. Madell, Carol Flexer and rising stars Jace Wolfe and Erin C. Schafer have compiled an impressive compendium of basic to complex diagnostic cases, covering the most salient topics in the field. The book effectively bridges the gap between content knowledge and clinical application, enabling readers to put acquired theory into active practice by engaging in problem-based learning. Key Features - All cases include key information for diagnosing and managing pediatric patients: clinical history, audiologic testing, evaluative reader questions, thought-provoking answers, definitive diagnosis, recommended treatment options, and final outcome - Expanded use of cochlear implants including implant performance issues - Overcoming challenges from family non-compliance and complicated mapping to professional collaboration and multidisciplinary assessments. Paired with the best-selling textbook Pediatric Audiology: Diagnosis, Technology, and Management, Third Edition, this robust classroom duo is an essential resource for instructors and students alike. Acquire in-depth knowledge from the textbook, apply it to practical case studies, and achieve deeper understanding of the full spectrum of pediatric audiology"--Provided by publisher.Digital Access Thieme MedOne ComSci [2020]
- ArticlePan WW, Li JD, Huang S, Papadimos TJ, Pan ZK, Chen LY.J Biol Chem. 2010 Nov 05;285(45):34348-54.In the host immune system, leukocytes are often exposed to multiple inflammation inducers. NF-κB is of considerable importance in leukocyte function because of its ability to activate the transcription of many proinflammatory immediate-early genes. Tremendous efforts have been made toward understanding how NF-κB is activated by various inducers. However, most research on NF-κB regulation has been focused on understanding how NF-κB is activated by a single inducer. This is unlike the situation in the human immune system where multiple inflammation inducers, including both exogenous and endogenous mediators, are present concurrently. We now present evidence that the formylated peptide f-Met-Leu-Phe (fMLP), a bacterial chemoattractant, synergizes with TNFα to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. The mechanism of synergistic activation of NF-κB by bacterial fMLP and TNFα may be involved in the induction of RelA acetylation, which is regulated by p38 MAPK. Thus, this study provides direct evidence for the synergistic induction of NF-κB-dependent inflammatory responses by both exogenous and endogenous inducers. The ability of fMLP to synergize with TNFα and activate NF-κB represents a novel and potentially important mechanism through which bacterial fMLP not only attracts leukocytes but also directly contributes to inflammation by synergizing with the endogenous mediator TNFα.
- ArticleRoca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ.J Biol Chem. 2009 Dec 04;284(49):34342-54.CCL2 and interleukin (IL)-6 are among the most prevalent cytokines in the tumor microenvironment, with expression generally correlating with tumor progression and metastasis. CCL2 and IL-6 induced expression of each other in CD11b(+) cells isolated from human peripheral blood. It was demonstrated that both cytokines induce up-regulation of the antiapoptotic proteins cFLIP(L) (cellular caspase-8 (FLICE)-like inhibitory protein), Bcl-2, and Bcl-X(L) and inhibit the cleavage of caspase-8 and subsequent activation of the caspase-cascade, thus protecting cells from apoptosis under serum deprivation stress. Furthermore, both cytokines induced hyperactivation of autophagy in these cells. Upon CCL2 or IL-6 stimulation, CD11b(+) cells demonstrated a significant increase in the mannose receptor (CD206) and the CD14(+)/CD206(+) double-positive cells, suggesting a polarization of macrophages toward the CD206(+) M2-type phenotype. Caspase-8 inhibitors mimicked the cytokine-induced up-regulation of autophagy and M2 polarization. Furthermore, E64D and leupeptin, which are able to function as inhibitors of autophagic degradation, reversed the effect of caspase-8 inhibitors in the M2-macrophage polarization, indicating a role of autophagy in this mechanism. Additionally, in patients with advanced castrate-resistant prostate cancer, metastatic lesions exhibited an increased CD14(+)/CD206(+) double-positive cell population compared with normal tissues. Altogether, these findings suggest a role for CCL2 and IL-6 in the survival of myeloid monocytes recruited to the tumor microenvironment and their differentiation toward tumor-promoting M2-type macrophages via inhibition of caspase-8 cleavage and enhanced autophagy.
- ArticleHomma K, Saito J, Ikebe R, Ikebe M.J Biol Chem. 2001 Sep 07;276(36):34348-54.Myosin X is a member of the diverse myosin superfamily that is ubiquitously expressed in various mammalian tissues. Although its association with actin in cells has been shown, little is known about its biochemical and mechanoenzymatic function at the molecular level. We expressed bovine myosin X containing the entire head, neck, and coiled-coil domain and purified bovine myosin X in Sf9 cells. The Mg(2+)-ATPase activity of myosin X was significantly activated by actin with low K(ATP). The actin-activated ATPase activity was reduced at Ca(2+) concentrations above pCa 5 in which 1 mol of calmodulin light chain dissociates from the heavy chain. Myosin X translocates F-actin filaments with the velocity of 0.3 microm/s with the direction toward the barbed end. The actin translocating activity was inhibited at concentrations of Ca(2+) at pCa 6 in which no calmodulin dissociation takes place, suggesting that the calmodulin dissociation is not required for the inhibition of the motility. Unlike class V myosin, which shows a high affinity for F-actin in the presence of ATP, the K(actin) of the myosin X ATPase was much higher than that of myosin V. Consistently nearly all actin dissociated from myosin X in the presence of ATP. ADP did not significantly inhibit the actin-activated ATPase activity of myosin X, suggesting that the ADP release step is not rate-limiting. These results suggest that myosin X is a nonprocessive motor. Consistently myosin X failed to support the actin translocation at low density in an in vitro motility assay where myosin V, a processive motor, supports the actin filament movement.