MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored. METHODS: We performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties of MACC1 overexpressing GBM cells. We quantified MACC1 dependent dynamics of 3D aggregate formation. For mechanistic studies we measured the expression of key adhesion molecules using qRT-PCR, and MACC1 dependent changes in short term adhesion to fibronectin and laminin. We then determined changes in sub-cellular distribution of integrins and actin in dependence of MACC1, but also in microtubule and intermediate filament organization. RESULTS: MACC1 increased the migratory speed and elastic modulus of GBM cells, but decreased cell-cell adhesion and inhibited the formation of 3D aggregates. These effects were not associated with altered mRNA expression of several key adhesion molecules or altered short-term affinity to laminin and fibronectin. MACC1 did neither change the organization of the microtubule nor intermediate filament cytoskeleton, but resulted in increased amounts of protrusive actin on laminin. CONCLUSION: MACC1 overexpression increases elastic modulus and migration and reduces adhesion of GBM cells thereby impeding 3D aggregate formation. The underlying molecular mechanism is independent on the organization of microtubules, intermediate filaments and several key adhesion molecules, but depends on adhesion to laminin. Thus, targeting re-organization of the cytoskeleton and cell motility via MACC1 may offer a treatment option to impede GBM spreading

Design of an expression system for rapid production of tri-functional antibody substitution of hybrid hybridoma technology

Tri-functional antibodies, as an effective novel tumor targeting agents, are composed of anti-CD3 rat IgG2b and an anti-tumor antigen antibody. We have intended to develop a novel drug system to induce the apoptosis of HER2-expressing tumor cells, activate and engage cytotoxic T lymphocytes, natural killer cells, and macrophages. In addition, the drug can inhibit programmed death ligand 1 (PDL-1)-expressing tumor cells. We have designed a mammalian vector system suitable to express the trifunctional antibody composed of antiHER2�human-CD80: human-IgG1Fc antibody. This antibody contains four chains of anti-HER2/CL, anti-HER2/CH1-3, B7.1/CL, and B7.1/CH1-3 within the human IgG1 framework and so the vector system will simultaneously express the four chains. The amino acid/nucleotide sequences datasets were retrieved from the GenBank, UniProtKB and PDB databases. The heavy and light chains variable domain framework regions and complementarity determining regions of scA21 antibody were determined by IMGT/V-QUEST and Paratome software. The amino acid sequences of tri-functional antibody chains manually were assembled and converted to DNA sequences by sequence manipulation suite software. The adapting codon usage of these DNA sequences was performed by JCAT software. Finally, the secondary structures of obtained RNAs from the DNAs were individually analyzed by RNAfold program. The Prodigy equilibrium dissociation constant, a ratio of koff/kon, between the antibody and its antigen for hantiHER2VHCH-HER2, hantiHER2VLCL-HER2, CD80CH-CD28, and CD80CL-CD28 were equal to 3.60E-10, 3.10E-9, 1.10E-8 and 2.70E-10; respectively. These findings were confirmed the composition and nano-molar affinity of the respective constructs. A single specific no-cloning expression vector, pHuchiTriomAb, was designed in silico with a desirable length of 8.292 Kbps and bidirectional expression potential for the four chimeric antibody chains. This construct was designed, and gene codon usage adapted to be expressed within CHO cells and secreted a trifunctional antibody into the cell culture medium by interleukin 21 signal peptide.This robust expression system for rapid production of tri-functional antibody has been designed to substitute hybrid hybridoma technology (quadroma and trioma)with the facilitated purification of the trifunctional antibody from the antibody variants. © 2018 Tehran University of Medical Sciences. All rights reserved

Charged BTZ-like Black Holes in Higher Dimensions

Motivated by many worthwhile paper about (2 + 1)-dimensional BTZ black holes, we generalize them to to (n + 1)-dimensional solutions, so called BTZ-like solutions. We show that the electric field of BTZ-like solutions is the same as (2 + 1)-dimensional BTZ black holes, and also their lapse functions are approximately the same, too. By these similarities, it is also interesting to investigate the geometric and thermodynamics properties of the BTZ-like solutions. We find that, depending on the metric parameters, the BTZ-like solutions may be interpreted as black hole solutions with inner (Cauchy) and outer (event) horizons, an extreme black hole or naked singularity. Then, we calculate thermodynamics quantities and conserved quantities, and show that they satisfy the first law of thermodynamics. Finally, we perform a stability analysis in the canonical ensemble and show that the BTZ-like solutions are stable in the whole phase space.Comment: 5 pages, two column format, one figur

Fabrication of UV/ TiO2 nanotubes / Pd system by electrochemical anodization for furfural photocatalytic degradation

The aim of this study was to degrade furfural by a new nanotube system. To degrade some organic pollutants as well as to reduce the amount of furfural which is a well-known pollutant in oil industry, the photocatalytic process along with ultraviolet (UV) irradiation may be employed. In this study, the UV/TiO2/Pd system in which the nanoparticles of palladium doped into the titanium dioxide was proposed for degradation of furfural. The rate of furfural decomposition in the proposed system was more than that of the system without TiO2 foils due to the degradable reactions. The experimental results demonstrate that the maximum degradation occurs at a distinct pH and specific temperature under the UV irradiation. After 100-minute UV-irradiation duration, the maximum and minimum degradations were 97.8% (pH 3), and 95.8% (pH 12), respectively. Also, the degradation values were as parabolic function at the pH values. The values of efficiency of decomposition for this irradiation duration at optimum pH 3 were 96.7% and 98.5% at 30◦C and 40◦C, respectively. Also, the minimum degradation under photolysis was 93.52% at 30oC under 20-minute UV-irradiation duration. Furthermore, while the irradiation duration was 70-75 min, the degradation values were independent of pH approximately. The difference between the degradation values at 30 and 40◦C was decreased with increasing the UV-irradiation duration till 60min, and then this difference was increased with increasing the UV-irradiation duration

Logarithmic correction to the Cardy-Verlinde formula in Topological Reissner-Nordstr\"om de Sitter Space

In this paper we compute leading order correction due to small statistical fluctuations around equilibrium, to the Cardy-Verlinde entropy formula (which is supposed to be an entropy formula of conformal field theory in any dimension) of a Topological Reissner-Nordstrom black hole in de Sitter space.Comment: 10 pages, no figure,LaTe

Fragmented QRS and subclinical left ventricular dysfunction in individuals with preserved ejection fraction: A speckle-tracking echocardiographic study

Introduction: Fragmented QRS (fQRS) complex on routine 12-lead electrocardiogram (ECG) predicts adverse outcomes in patients with cardiovascular diseases. In addition, it has been found to be associated with subclinical myocardial dysfunction in chronic diseases. We sought to investigate the relationship between the presence of fQRS with the myocardial functions in individuals free from known systemic cardiovascular diseases. Methods: In a case-control study, we evaluated normal individuals from March 2017 to February 2018. All participants underwent a 2-dimensional transthoracic echocardiographic examination using tissue Doppler imaging (TDI) and speckle-tracking echocardiography. In addition, all participants were examined using a 12-lead surface ECG, and patients with fQRS and a group of age- and sex-matched controls without fQRS were enrolled in our study. Results: The patients' mean age was 40.3 ± 10.7 and 35.4 ± 11.2 years in fQRS-positive and fQRS-negative groups, respectively (P =.110). Patients with fQRS had significantly lower values of apical left ventricular global longitudinal strain (LV GLS) in 2-chamber (16.9 ± 2.5 vs. 20.5 ± 3.3, P <.001), 4-chamber (16.9 ± 3.4 vs. 20.1 ± 3, P =.001), LAX views (17.7 ± 2.8 vs. 20.8 ± 3.5, P =.001), and averaged LV GLS (17 ± 2.6 vs. 20.4 ± 2.7, P <.001) values compared to patients without fQRS. In a multivariate analysis, averaged LV GLS and smoking history were independent predictors for positive fQRS. Conclusion: The presence of fQRS on 12-lead ECG in healthy population was associated with lower values of LV GLS compared to normal individuals without fQRS. © 2019 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society

A study on distribution and biomass estimination of seaweeds in coastal and its islands

Distribution and biomass of seaweeds in the Persian Gulf and its islands were assessed monthly during low tide from July 2001 to August 2003. Ten stations were defined in the study area and random spots along a transect vertical to the coastline were selected to carry out the sampling. Six stations were located in the coastal waters and four others were close to the islands. Samples were taken in quadrats 0.25 square meter in size (0.5mx0.5m). As a result, 77 species belonging to 4 division of seaweeds were identified. Rhodophyta was represented by 38 species, Chlorophyta had 21 species followed by 17 species of Phaeophyta and only I species of Cyanophyta. The highest and lowest seaweed diversity was seen around Larak Island and Michael station with 74 and 31 species respectively. Although some species such as Gracilaria corticata, Gelidiella acerosa, Laurencia snyderia, Colpomenia sinousa, Padina australis and Diciyosphaeria covernosa were abundant in all stations during the study, some species were absent from some stations. Thrbinaria conoiedes was only seen in Larak island, Spatoglassum variable and Steochospermum marginatum were present only in Larak and Qeshem islands, Codium papilatum and Ulva spp. were spotted only in Larak and Hormoz islands, and Sargassum ilicifolium was detected only in Bandar Lengeh, Shiyo, Larak and Qeshem islands. The maximum and minimum algal biomass (wet weight) was recorded in Bandar Lengeh with 1.058gram^2 and Qeshem island with 391gram'2 and there was significant difference between the two stations (P<0.05). Also the maximum algal biomass was recorded in summer (1466gr.m^2) in Tahoneh-Gorzeh and the minimum biomass (130gram^2) in Qeshem islands. The highest biomass was recorded for the brown algae division (824gram^2) in Bandar Lengeh and the minimum biomass was seen for the green algae division (26gram^2) in Hormoz. and Qeshm islands. The maximum biomass was 755gram in summer for red algae, 1160gram^-2 in Spring for brown algae and 519gram^2 in Summer for green algae

Effect of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in patients with an implantable cardioverter-defibrillator

Background: Cardiac resynchronization therapy (CRT) reduces mortality in selected patients with heart failure. However, this result may not be entirely related to the beneficial hemodynamic effects of CRT. Objectives: The purpose of this study was to assess retrospectively the effect of CRT on the incidence of appropriate therapy in patients with an implantable cardioverter-defibrillator (ICD). Methods: Sixty-five patients (48 men and 17 women; mean age 58 ± 13 years) with an ICD (31 biventricular, 34 dual-chamber) were included in the study. Clinical, ECG, and ICD stored data and electrograms were collected. Results: Biventricular and dual-chamber ICDs were implanted in 31 and 34 patients, respectively, who had either ischemic (n = 36) or dilated cardiomyopathy (n = 29). Thirty-two (49) patients received �1 appropriate ICD therapy during follow-up of 11 ± 8 months. Thirty-five percent and 62 of patients with biventricular (n = 11) and dual-chamber ICDs (n = 21), respectively, received appropriate ICD therapy during the follow-up period (odds ratio = 0.340, P = .048). Stratifying the patients according to underlying heart disease and ejection fraction resulted in an adjusted odds ratio = 0.239 (P = .029). Comparing the rate of �1 appropriate ICD therapy between the two groups by Kaplan-Meier analysis and the log rank test resulted in P = .027. Conclusion: In this retrospective analysis, biventricular pacing was associated with a decreased incidence of sustained ventricular arrhythmias requiring ICD therapy. The antiarrhythmic effect of biventricular pacing could contribute to the reduction in mortality reported in recent large-scale clinical trials on CRT. However, further prospective studies are warranted to clarify this issue. © 2005 Heart Rhythm Society. All rights reserved

Effect of conduction mode and location on electrophysiologic characteristics of accessory pathways

The conduction properties of accessory pathways (APs) are independent of location and conduction mode (except in patients with multiple, Mahaim, and slowly conducting APs). Patients with right-sided APs show higher rates of atrial fibrillation and longer arrhythmia cycle length due to slower anterograde conduction over the atrioventricular node during atrioventricular reentrant tachycardia. © 2005 by Excerpta Medica Inc

Heart rate variability: Does it change after RF ablation of reentrant supraventricular tachycardia?

Background: Following RF ablation of reentrant supraventricular tachycardia, inappropriate sinus tachycardia may occur. Local parasympathetic denervation is a possible mechanism for these rhythm disturbances. The purpose of this study was to determine the incidence of sinus tachycardia and to determine the relation between endocardial lesions at different ablation sites and alterations in autonomic tone in several different groups of patients with supraventricular tachycardia, using techniques of heart rate variability analysis. Methods: The subjects of this study were 75 patients (48 women, 27 men) with a mean age of 39.99 (SD = 13.39). They underwent RF ablation of AV nodal slow pathways (40 cases), posteroseptal APs (23 cases), left lateral and right free wall APs (12 cases) because of symptomatic tachycardias. The mean sinus rate and time domain (standard deviation of RR intervals and root mean square of differences of adjacent RR intervals) and frequency domain (low frequency, high frequency and low frequency/high frequency ratio) analyses of heart rate variability were obtained by use of 24 hour Holter monitoring before and 1 month after ablation compared with pre-ablation values. Results: Analysis of 24 hour ambulatory Holter-monitors, performed 1 month after RF ablation, showed no significant changes in time and frequency domain parameters of heart rate variability in different groups. A significant increase in mean heart rate was noted after RF ablation at AV nodal slow pathway group and left freewall/right free wall accessory pathways group. Patients undergoing RF ablation of right or left posteroseptal accessory pathways had no significant increase in the mean heart rate. Conclusion: In summary, an increase in sinus tachycardia may be initiated by RF ablation of atrioventricular reentrant tachycardia (AVNRT) and right free wall or left free wall accessory pathways. This finding shows that the modifications of heart rate are not directly related to the posteroseptal region or to the accessory pathways. © 2006 Springer Science + Business Media, Inc