Changes In Adhesive Properties Research Articles

Interfacial adhesion between recycled asphalt binder and aggregates considering aggregate surface anisotropy: A molecular dynamics simulation

In this study, the interfacial adhesion properties between reclaimed asphalt binder and aggregates were investigated using the molecular dynamics (MD) simulation method. Surface free energy theory (SFE) was applied to analyze the changes in adhesion properties before and after asphalt binder reclamation. The asphalt binder model was constructed from the four components of asphalt binder and validation of the model was carried out. The five common crystalline surfaces of two types of aggregates were sliced. The asphalt binder-aggregate interface was modelled to investigate the effect of the anisotropic surface of the aggregates on the adhesion of the asphalt binder. The adhesion properties of the recycled asphalt binder-aggregate interface were characterized from micro and multiscale simulations using the work of adhesion and relative concentration. Results showed that the rejuvenators enhanced the adhesive properties of the asphalt binder by rebalancing the components and adding the light components lost from aging. Surface anisotropy had significant effect on the bonding at the asphalt binder-aggregate interface because α-SiO2 bonded to acid surfaces less strongly than CaCO3 linked to alkali surfaces. Van der Waals forces dominated the adhesion energy in the α-SiO2-asphalt binder interfacial model system. In the CaCO3-asphalt-binder interface model system, the combined effect of van der Waals forces and the CaCO3 surface void reduced the adhesion energy of the aggregate surface to the asphalt binder.

Micro-characterization of the adhesion properties and mechanisms at the asphalt-silica aggregate interface under combined thermal-oxygen aging and chloride salt erosion

In this investigation, various Atomic Force Microscopy (AFM) probes were used to characterize changes in the adhesion properties of aged asphalt under different concentrations of chloride salt. The characterization included analyzing the surface morphology, roughness parameters, height-height correlation function (HHCF), and force-distance curves of the asphalt. Additionally, Molecular Dynamics (MD) simulation was employed to reveal the underlying mechanisms that govern changes in adhesion properties between aged asphalt and aggregate when subjected to chloride salt erosion. Interfacial erosion and internal erosion models were constructed to facilitate a comprehensive analysis from multiple perspectives. The results demonstrate that chloride salts interact with the interface between asphalt and silica aggregates, engaging in competitive adsorption with the asphalt. The strength of this competitive adsorption is influenced by the constituents of the asphalt and the concentration gradient of chloride salts both within and outside the asphalt matrix. Under this concentration gradient, polar components are attracted to the asphalt surface by chloride ions, forming triangular adsorption structures with water molecules and aggregates such as asphaltene. Components with lower polarity exhibit distinct distributions and diffusion states due to variations in molecular weight and spatial configuration. As the concentration of chloride salts increases, the concentration gradient intensifies, resulting in enhanced transformations, migrations, and dissolutions of asphalt components. Consequently, the micro-morphology of the asphalt tends to smoothen, the HHCF undergoes significant modifications, roughness decreases, and the adhesion performance between asphalt and aggregate weakens. Moreover, at higher concentrations, the formation of precipitated chloride salt crystals disrupts the continuity of the asphalt, further compromising interfacial adhesion performance. This study is expected to provide theoretical guidance for the modification of asphalt and the improvement of asphalt pavement lifespan in complex service environments.

Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice.

Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE−/−) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFβ, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFβ) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE−/− mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFβ at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE−/− mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFβ increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.

Hypoxic Storage of Red Blood Cells: Assessment of Adhesion Properties Using a Standardized Endothelium-on-a-Chip Microfluidic Platform

Background: Blood transfusions are routine medical procedures in which stored blood or blood products (i.e., red blood cells, RBCs) are given to the patient to prevent adverse health outcomes due to acute or chronic anemia. The current regulations require RBCs to be stored at 4 ºC not more than 42 days before a transfusion. However, RBCs undergo extensive rheological changes during storage and may contribute to complications associated with transfusion. Hemanext has recently introduced an innovative storage system to ameliorate such storage lesions, in which RBCs are stored in a hypoxic environment, and thus they are exposed to much lower oxidative stress during storage. In this study, we report the changes in adhesion properties of stored RBCs to human endothelial cells following a 42-day storage in normoxia vs hypoxia, using a standardized endothelialized microfluidic platform: Endothelium-on-a-chip.Methods: Two units of 1-day old blood type O positive leukocyte reduced RBCs in additive solution were pooled and divided into equal aliquots (300mL each) A and B. Unit A was stored under conventional normoxic storage condition at 4°C for 42 days. Unit B was deoxygenated so that the percent oxygen saturation of the hemoglobin was less than 20%. The deoxygenated RBCs were stored in an oxygen impermeable storage bag for 42 days at 4°C. Adhesion levels were tested at the beginning (baseline, Week 1) and the end of the storage period (Week 6). To conduct the adhesion experiments, human umbilical vein endothelial cells (HUVECs) were first cultured within microfluidic channels under flow for at least 48 hours. Next, the HUVECs were treated with 40 µM heme for 4 hours at 37 ºC [1]. RBCs were centrifuged to remove the storage buffer and resuspended in basal cell culture medium (EGM, Lonza, Morristown, USA) supplemented with 10 mM HEPES at a hematocrit of 40%. A 15 µl of RBC solution was then injected over heme-activated HUVECs at a shear stress of 1 dyne/cm 2 followed by a 10-minute rinse with fresh basal culture medium to remove non-adherent RBCs. At the end of the experiment, adherent erythrocytes were manually quantified. Control experiments were conducted with non-activated HUVECs.Results: We found that RBCs that were stored under conventional normoxic condition displayed higher adhesion to heme-activated HUVECs than hypoxic condition as illustrated in Figure 1A and 1B. The baseline adhesion levels (Week 1) to non-activated HUVECs (control) were negligible (Fig. 1C, normoxia: 13±6; hypoxia: 18±10, p>0.05) while both cell populations had considerable adhesion levels to heme-activated HUVECs at baseline (Fig. 1C, normoxia: 372±59; hypoxia: 335±37). Following a 6-week storage, adhesion of RBCs stored in normoxia to heme-activated HUVECs was higher compared to those stored in hypoxic conditions while the p-value was not significant, which was likely due to the limited sample size (Fig. 1C, 1782±519 vs 594±55, p=0.08, N=3). These results suggest that storage-mediated RBC adhesion to heme-activated HUVECs may be ameliorated by the novel hypoxic-storage condition.Discussion: This study showed a decrease in the adhesion of hypoxic RBCs to heme-activated HUVECs when compared to conventionally stored RBCs for transfusion. This result suggests that hypoxic RBCs may reduce the risk of developing vaso-occlusion (VOC) after RBC transfusion in patients such as in sickle cell disease where adhesion to heme-activated HUVECs has been implicated in the pathogenesis of VOC [1].Acknowledgements: This work was funded by Hemanext. The authors would like to thank the Ohio Third Frontier Technology Validation and Start-up Fund (TVSF) and National Science Foundation Phase-I Small Business Technology Transfer (STTR) award, which supported this work in part. Stored RBCs were donated by Hemanext.Reference:1. Kucukal, E., et al., American Journal of Hematology, 2018. 93(8): p.1050-1060 [Display omitted] DisclosuresKucukal: BioChip Labs: Current Employment, Patents & Royalties. Kocevar: BioChip Labs: Current Employment. Nayak: BioChip Labs: Current Employment. Sowemimo-Coker: Hemanext: Current Employment. Zak: BioChip Labs: Current Employment, Current holder of stock options in a privately-held company; XaTek: Current Employment, Current holder of stock options in a privately-held company; TecTraum Inc: Current Employment, Current holder of stock options in a privately-held company. Omert: Hemanext: Current Employment. Gurkan: Biochip Labs: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Dx Now Inc.: Patents & Royalties; Xatek Inc.: Patents & Royalties.

Cellular junction and mesenchymal factors delineate an endometriosis-specific response of endometrial stromal cells to the mesothelium

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation.

Abstract 2989: Peristalsis-like deformations influence tumor cell intravasation and metabolic reprogramming in a novel colorectal cancer-on-chip model

Abstract Colorectal cancer (CRC) is one of the deadliest cancers in the U.S., yet we still understand very little about the mechanisms behind this disease. Therefore, we are developing a CRC-Chip model that recapitulates the complex nature of cancer progression in order to increase our understanding of CRC and accelerate the discovery of new treatments. The organ-on-chip technology developed by Emulate, Inc. maintains physiologically relevant aspects of organ structure and function by incorporating tissue compartments and mechanical forces to mimic in vivo peristalsis and fluid flow. The CRC-Chip consists of two microfluidic compartments separated by a porous membrane, with endothelial cells in the bottom channel and normal colon epithelial cells plus fluorescently-labeled CRC cell lines in the top channel. Via confocal microscopy, We observed monitored cancer cells intravasating from the epithelial compartment into the blood vessel compartment via confocal microscopy, mimicking early metastatic spread. A unique advantage of this system is the ability to interrogate how mechanical forces influence cancer cell intravasation. The presence of peristalsis-like deformations increased the invasion rate of cancer cells. To further investigate the increased aggressiveness, viable tumor cells were collected from the effluent of the blood vessel channel reservoir. These shedded circulating cells, representing the invaded CRC cells, showed markers of epithelial to mesenchymal transition (EMT) induction and changes in adhesive properties. To further understand how peristalsis influences CRC cells, we performed mass-spectrometry based metabolomics on the effluent from the top and bottom channels of CRC-chips in the presence or absence of peristalsis-like motions. The differentially expressed metabolites, when mapped with Ingenuity Pathway Analysis, indicated changes primarily to amino acid/central carbon metabolism in the epithelial channel and differential lipid profiles in the endothelial channel when peristalsis was present. Given a majority of CRC metastases occur in the liver, we optimized the coupling of our CRC-Chip with a normal Liver-Chip model to better understand how intravasated tumor cells from a peristaltic colon environment colonize a healthy liver. This work illuminates the important role of mechanical forces in CRC progression, a currently understudied aspect of the tumor microenvironment. Further insights into a better understanding of how peristalsis increases the metastatic spread of CRC cells may lead to the discovery of novel therapeutic strategies that can halt critical steps in tumor progression. Citation Format: Carly Strelez, Sujatha Chilakala, Ah Young Yoon, Kimya Ghaffarian, Danielle Hixon, Roy Lau, Jonathan E. Katz, Shannon M. Mumenthaler. Peristalsis-like deformations influence tumor cell intravasation and metabolic reprogramming in a novel colorectal cancer-on-chip model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2989.

Effects of working time on properties of a soybean meal-based adhesive for engineered wood flooring

ABSTRACT Soybean meal-based adhesives (SMAs) commercially applied in wood-based composites require stable bonding properties. However, the structure and properties of SMAs are not as stable as synthetic resins, which significantly affect their performances. In this study, the structure–property evolution of a SMA with working time was systematically investigated. The findings revealed that the secondary structure, microstructure, crosslinking density, zeta potential, nitrogen solubility index, viscosity, wood permeability, and bonding properties of SMA considerably vary with working time. The changes in adhesive properties were correlated with the dissolution of SM particles in crosslinker solution and the increased pre-curing of liquid SMA with working time resulting from the crosslinking reactions between the dissolved SM and the crosslinker. Preferably, SMA at the working time between 0.5 h and 3 h since the mixing of soybean meal flour with crosslinker solution, should be used in order to ensure the desired water resistance of plywood panels for engineered wood flooring. And an application strategy was proposed to ensure the required water resistance of plywood panels for manufacturing engineered wood flooring.

Synthesis of Photo-degradable Polyphthalaldehyde Macromonomer and Adhesive Property Changes of its Copolymer with Butyl Acrylate on UV-irradiation

We prepared a new polyphthalaldehyde (PPA) macromonomer by introducing a polymerizable methacryloyl group at the terminal of PPA main-chain. Resulting macromonomer was copolymerized with butyl acrylate to obtain pressure-sensitive adhesives (PSAs). We also compared the behavior of the copolymers with those of polymer blends of poly(butyl acrylate) and linear PPA polymers to clarify the role of polymerization. Higher peel strengths were observed for copolymers than those of corresponding polymer blends. As an increase in irradiation time, the strength generally decreased, although once increased for the copolymer films at the early stage. These results suggest that the introduction and the depolymerization of PPA side-chains caused drastic changes in adhesive properties.

Changes of adhesion properties for negative electrode and positive electrode under wet conditions and different states of charge

Debonding often occurs in flexible batteries due to mechanical and electrochemical coupling during service. Debonding of electrode will seriously affect the capacity and life of the battery, and even cause a short circuit inside the battery, resulting in spontaneous combustion. Here, the adhesion performance between the electrode sheet and the active material are investigated under the electrolyte environment and different states of charge (SOCs). A small stretcher loading device is used to perform stripping experiments on positive electrodes and negative electrodes in a glove box filled with argon to obtain the peel strength. The binders used in the positive and negative electrodes in this paper are polyvinylidene fluoride (PVDF) and Styrene-Butadiene Rubber/Carboxymethyl Cellulose (SBR/CMC). Compared with the electrode sheet without electrolyte, the peel strength of the positive electrode and negative electrode is decreased by 89.7% and 46.3%, respectively. The significant reduction in peel strength is due to the swelling effect of the electrolyte on the binder. The scanning electron microscope observation shows that there is a large number of active material particles at the interface of the positive electrode and the negative electrode after peeling. Additionally, the peel strength of the positive electrode was increases slightly with the increase of SOC and the added value is 14.8%. But the peel strength of negative electrode decreased with the increase of SOC and the added value is 47.6%. These results play an essential role in evaluating the interface peel strength of the electrode sheet in the different environment and designing electrochemical performance for batteries.

Anti-adhesion properties of aminopropanol derivative with N-alkylaryl radical KVM-194 against Pseudomonas aeruginosa

Introduction. The present study assessed Pseudomonas aeruginosa surface characteristics, motility and adhesion properties under the influence of 1-[4-(1,1,3,3-tetra methyl butyl) phenoxy]-3-(N-benzyl hexa methylene iminium)-2-propanol chloride (KVM-194).
 Material and methods. The clinical strain P. aeruginosa 449 was used in the study. The cell surface hydrophobicity (CSH) was evaluated by adhesion to solvent (MATS test). Swimming, swarming and twitching motility of P. aeruginosa were studied by standard methods in media with different agar contents. Cells ability to adhere to polystyrene was assessed by the Christensen method. The effect of KVM-194, meropenem and ciprofloxacin on hydrophobicity and motility was evaluated both at 0.5 or 2.0 minimal inhibitory concentrations (MIC), while on adhesion abilities – only 0.5×MIC.
 Results. It was shown that 0.5× MIC KVM-194 reduced CSH of P. aeruginosa (by 16%, p˂0.05), affected swimming motility, and decreased its adhesion to polystyrene. The most pronounced changes in adhesion properties were recorded after 3-5 hours of pre-treatment with this compound. Moreover, it was proven that sub-MICs of meropenem and ciprofloxacin did not alter bacterial cells hydrophobicity and had no significant influence on P. aeruginosa motility and adhesion properties.
 Conclusions. The present study suggested that KVM-194 affected the initial steps of P. aeruginosa biofilm formation and thus had tremendous potential for new antibiofilm agents’ development.

Functionalization of Neutral Polypropylene by Using Low Pressure Plasma Treatment: Effects on Surface Characteristics and Adhesion Properties.

Polyolefins are considered among the most difficult polymeric materials to treat because they have poor adhesive properties and high chemical barrier responses. In this paper, an in-depth study is reported for the low pressure plasma (LPP) treatment of neutral polypropylene to improve adhesion properties. Changes in wettability, chemical species, surface morphology and roughness of the polypropylene surfaces were evaluated by water contact angle measurement, X-ray photoelectron spectroscopy and, furthermore, atomic force microscopy (AFM). Finally, the bonded joints were subjected to tensile tests, in order to evaluate the practical effect of changes in adhesion properties. The results indicate that plasma is an effective treatment for the surface preparation of polypropylene for the creation of bonded joints: contact angles decreased significantly depending on the plasma-parameter setup, surface morphology was also found to vary with plasma power, exposure time and working gas.

Gender-related dimorphism of changes in adhesive properties of the vascular wall in the dynamics of surgical treatment of chronic generalized periodontitis

The purpose of the study was to reveal gender-related dimorphism of changes in adhesive properties of the vascular wall in the dynamics of surgical treatment of chronic periodontitis (CP). A total of 51 persons aged 24 to 39 years were examined, of which 20 were clinically healthy volunteers (10 men and 10 women) and 31 were patients with CP of moderate severity (14 men and 17 women). It has been shown that endothelial dysfunction is more pronounced in men than in women with CP. Surgical treatment of CP is accompanied by a reactive increase in the concentration of soluble forms of adhesive endothelial molecules in early postoperative period more pronounced in women. In the long-term period surgical treatment causes a decrease in the impairment of the endothelial adhesive properties in men to a lesser extent than in women.

Formation of copper sulfides on polypropylene matrix using various reducing agents

Layers of copper sulfides, CuxS, on the surface of a polypropylene film were formed by the sorption–diffusion method using two reducing agents – hydroquinone and hydroxylamine sulfate. The formed copper sulfide layers were investigated by UV/VIS, X-ray diffraction (XRD) and water contact angle measurements (WCA). The investigations confirmed that a layer of nonstoichiometric copper sulfide was formed on the surface of the polypropylene film. The water contact angle measurements revealed the change in adhesive properties of the samples after each treatment stage.

Microbial responses to transient shock loads of quaternary ammonium compounds with different length of alkyl chain in a membrane bioreactor

Extensive applications of quaternary ammonium compounds (QACs) in household and industrial products inevitably lead to their release into wastewaters; however, little attention has been paid to the acute effects on activated sludge. In this work, we investigated the responses of microorganisms in a membrane bioreactor (MBR) to transient shock loads of QACs with different alkyl chain length and their impacts on MBR performance. Results showed that QACs affected microbial viability and caused damage to key enzymes (e.g., ammonium monooxygenase and nitrite oxidoreductase), inhibiting organic matter degradation and nitrogen removal. The presence of QACs also caused negative influences on dehydrogenase activity, catalase and superoxide dismutase, thus increasing the production of reactive oxygen species. Moreover, QACs with longer alkyl chains and/or benzyl groups bonded to the nitrogen atom could induce a more severe damage to cell integrity and microbial viability. The interaction with QACs also induced the release of organic matters and the changes of adhesion properties of microbial products, resulting in aggravated membrane fouling in MBRs. Our results demonstrate the acute negative effects of QACs on activated sludge, and special attention should be paid to the performance of biological wastewater treatment processes subject to the shock loads of QAC-bearing industrial streams.

Effect of ampicillin on adhesive properties of bacteria examined by atomic force microscopy

Discovery of new antibacterial agents requires the development of novel techniques for bacteria surface characterization after treatment with antibiotics. In this study, we investigate the effect of ampicillin at MICs levels on adhesive properties of Gram-positive and Gram-negative bacteria, using atomic force microscopy (AFM). Our results revealed that the treatment leads to changes of bacterial surface properties, especially cell surface roughness. A nanomechanical alteration of the cells led to an increase of adhesive forces and rupture lengths. Changes in adhesive properties are determined not only by the modification of physicochemical cell properties but also by an increase in roughness, leading to an increase of the contact area with a cantilever tip. We discovered that the contribution of non-specific physicochemical interactions in the bacteria attachment to a substrate is not negligible and was significantly influenced by the presence of antibiotic. Ampicillin caused much greater change in the adhesion properties of Bacillus subtilis than Escherichia coli due to the mode of action of β-lactam antibiotic. Adhesion measurements may by a new way to investigate subtle changes of the bacterial surface properties caused by antibiotic, especially those targeting the bacterial cell wall. In contrast to nanoindentation assays, they provide information on adhesive properties of the bacteria surface.

Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC).

The connective tissue formed by extracellular matrix (ECM) rich in fibronectin and collagen consists a barrier that cancer cells have to overpass to reach blood vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by αvβ3 and α5β1 integrins through an RGD motif present in this ECM protein, thus making these receptors key targets for cell migration studies. Here we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of human fibroblasts (BJ) and oral squamous cancer cells (OSCC, SCC25) on a fibronectin-rich environment. Time-lapse images were acquired on fibronectin-coated glass-bottomed dishes. Migration speed and directionality analysis indicated that OSCC cells, but not fibroblasts, showed significant decrease in both parameters in the presence of DisBa-01 (1μM and 2μM). Integrin expression levels of the α5, αv and β3 subunits were similar in both cell lines, while β1 subunit is present in lower levels on the cancer cells. Next, we examined whether the effects of DisBa-01 were related to changes in adhesion properties by using paxillin immunostaining and total internal reflection fluorescence TIRF microscopy. OSCCs in the presence of DisBa-01 showed increased adhesion sizes and number of maturing adhesion. The same parameters were analyzed usingβ3-GFP overexpressing cells and showed that β3 overexpression restored cell migration velocity and the number of maturing adhesion that were altered by DisBa-01. Surface plasmon resonance analysis showed that DisBa-01 has 100x higher affinity for αvβ3 integrin than forα5β1 integrin. In conclusion, our results suggest that the αvβ3 integrin is the main receptor involved in cell directionality and its blockage may be an interesting alternative against metastasis.

Dynamic Patterns of Clonal Evolution in Tumor Vasculature Underlie Alterations in Lymphocyte-Endothelial Recognition to Foster Tumor Immune Escape.

Although tumor blood vessels have been a major therapeutic target for cancer chemotherapy, little is known regarding the stepwise development of the tumor microenvironment. Here, we use a multicolor Cre-dependent marker system to trace clonality within the tumor microenvironment to show that tumor blood vessels follow a pattern of dynamic clonal evolution. In an advanced melanoma tumor microenvironment, the vast majority of tumor vasculature clones are derived from a common precursor. Quantitative lineage analysis reveals founder clones diminish in frequency and are replaced by subclones as tumors evolve. These tumor-specific blood vessels are characterized by a developmental switch to a more invasive and immunologically silent phenotype. Gene expression profiling and pathway analysis reveals selection for traits promoting upregulation of alternative angiogenic programs such as unregulated HGF-MET signaling and enhanced autocrine signaling through VEGF and PDGF. Furthermore, we show a developmental switch in the expression of functionally significant primary lymphocyte adhesion molecules on tumor endothelium, such as the loss in expression of the mucosal addressin MAdCAM-1, whose counter receptor a4β7 on lymphocytes controls lymphocyte homing. Changes in adhesive properties on tumor endothelial subclones are accompanied by decreases in expression of lymphocyte chemokines CXCL16, CXCL13, CXCL12, CXCL9, CXCL10, and CCL19. These evolutionary patterns in the expressed genetic program within tumor endothelium will have both a quantitative and functional impact on lymphocyte distribution that may well influence tumor immune function and underlie escape mechanisms from current antiangiogenic pharmacotherapies.

The raspberry Gene Is Involved in the Regulation of the Cellular Immune Response in Drosophila melanogaster.

Drosophila is an extremely useful model organism for understanding how innate immune mechanisms defend against microbes and parasitoids. Large foreign objects trigger a potent cellular immune response in Drosophila larva. In the case of endoparasitoid wasp eggs, this response includes hemocyte proliferation, lamellocyte differentiation and eventual encapsulation of the egg. The encapsulation reaction involves the attachment and spreading of hemocytes around the egg, which requires cytoskeletal rearrangements, changes in adhesion properties and cell shape, as well as melanization of the capsule. Guanine nucleotide metabolism has an essential role in the regulation of pathways necessary for this encapsulation response. Here, we show that the Drosophila inosine 5'-monophosphate dehydrogenase (IMPDH), encoded by raspberry (ras), is centrally important for a proper cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. Notably, hemocyte attachment to the egg and subsequent melanization of the capsule are deficient in hypomorphic ras mutant larvae, which results in a compromised cellular immune response and increased survival of the parasitoid.

Evaluation of Adhesive T-Joint Using Finite Element Analysis

This study evaluates the effect of temperature upon adhesive properties and behavior of adhesively bonded T-joint. Finite element analyses established the effect of this parameter on the durability joint and stress distribution within the adhesive layer. A series of temperatures and stress analyses using finite element analysis (FEA) has been conducted in the T-joint configuration for this purpose. The parametric studies on the FE model revealed that stress distributions are sensitive to the changes in adhesive properties due to changes in temperature. In general, stresses were reduced with changes in the temperature which resulted in the ability of the adhesive layer to undergo plastic deformation.

The Susd2 protein regulates neurite growth and excitatory synaptic density in hippocampal cultures.

Complement control protein (CCP) domains have adhesion properties and are commonly found in proteins that control the complement immune system. However, an increasing number of proteins containing CCP domains have been reported to display neuronal functions. Susd2 is a transmembrane protein containing one CCP domain. It was previously identified as a tumor-reversing protein, but has no characterized function in the CNS. The present study investigates the expression and function of Susd2 in the rat hippocampus. Characterization of Susd2 during development showed a peak in mRNA expression two weeks after birth. In hippocampal neuronal cultures, the same expression profile was observed at 15days in vitro for both mRNA and protein, a time consistent with synaptogenesis in our model. At the subcellular level, Susd2 was located on the soma, axons and dendrites, and appeared to associate preferentially with excitatory synapses. Inhibition of Susd2 by shRNAs led to decreased numbers of excitatory synaptic profiles, exclusively. Also, morphological parameters were studied on young (5DIV) developing neurons. After Susd2 inhibition, an increase in dendritic tree length but a decrease in axon elongation were observed, suggesting changes in adhesion properties. Our results demonstrate a dual role for Susd2 at different developmental stages, and raise the question whether Susd2 and other CCP-containing proteins expressed in the CNS could be function-related.