In vivo characterization of the novel ebolavirus Bombali virus suggests a low pathogenic potential for humans.

Ebolaviruses cause outbreaks of haemorrhagic fever in Central and West Africa. Some members of this genus such as Ebola virus (EBOV) are highly pathogenic, with case fatality rates of up to 90%, whereas others such as Reston virus (RESTV) are apathogenic for humans. Bombali virus (BOMV) is a novel ebolavirus for which complete genome sequences were recently found in free-tailed bats, although no infectious virus could be isolated. Its pathogenic potential for humans is unknown. To address this question, we first determined whether proteins encoded by the available BOMV sequence found in Chaerephon pumilus were functional in in vitro assays. The correction of an apparent sequencing error in the glycoprotein based on these data then allowed us to generate infectious BOMV using reverse genetics and characterize its infection of human cells. Furthermore, we used HLA-A2-transgenic, NOD-scid-IL-2γ receptor-knockout (NSG-A2) mice reconstituted with human haematopoiesis as a model to evaluate the pathogenicity of BOMV in vivo in a human-like immune environment. These data demonstrate that not only does BOMV show a slower growth rate than EBOV in vitro, but it also shows low pathogenicity in humanized mice, comparable to previous studies using RESTV. Taken together, these findings suggest a low pathogenic potential of BOMV for humans.

Soft wetting with (a)symmetric Shuttleworth effect.

The wetting of soft polymer substrates brings in multiple complexities when compared with the wetting on rigid substrates. The contact angle of the liquid is no longer governed by Young's Law, but is affected by the substrate's bulk and surface deformations. On top of that, elastic interfaces exhibit a surface energy that depends on how much they are stretched-a feature known as the Shuttleworth effect (or as surface-elasticity). Here, we present two models through which we explore the wetting of drops in the presence of a strong Shuttleworth effect. The first model is macroscopic in character and consistently accounts for large deformations via a neo-Hookean elasticity. The second model is based on a mesoscopic description of wetting, using a reduced description of the substrate's elasticity. While the second model is more empirical in terms of the elasticity, it enables a gradient dynamics formulation for soft wetting dynamics. We provide a detailed comparison between the equilibrium states predicted by the two models, from which we deduce robust features of soft wetting in the presence of a strong Shuttleworth effect. Specifically, we show that the (a)symmetry of the Shuttleworth effect between the 'dry' and 'wet' states governs horizontal deformations in the substrate. Our results are discussed in the light of recent experiments on the wettability of stretched substrates.

Microbial diversity characterization of seawater in a pilot study using Oxford Nanopore Technologies long-read sequencing.

OBJECTIVE: Currently the majority of non-culturable microbes in sea water are yet to be discovered, Nanopore offers a solution to overcome the challenging tasks to identify the genomes and complex composition of oceanic microbiomes. In this study we evaluate the utility of Oxford Nanopore Technologies (ONT) sequencing to characterize microbial diversity in seawater from multiple locations. We compared the microbial species diversity of retrieved environmental samples from two different locations and time points. RESULTS: With only three ONT flow cells we were able to identify thousands of organisms, including bacteriophages, from which a large part at species level. It was possible to assemble genomes from environmental samples with Flye. In several cases this resulted in > 1 Mbp contigs and in the particular case of a Thioglobus singularis species it even produced a near complete genome. k-mer analysis reveals that a large part of the data represents species of which close relatives have not yet been deposited to the database. These results show that our approach is suitable for scalable genomic investigations such as monitoring oceanic biodiversity and provides a new platform for education in biodiversity.

Failure of Local Thermal Equilibrium in Quantum Friction.

Recent progress in manipulating atomic and condensed matter systems has instigated a surge of interest in nonequilibrium physics, including many-body dynamics of trapped ultracold atoms and ions, near-field radiative heat transfer, and quantum friction. Under most circumstances the complexity of such nonequilibrium systems requires a number of approximations to make theoretical descriptions tractable. In particular, it is often assumed that spatially separated components of a system thermalize with their immediate surroundings, although the global state of the system is out of equilibrium. This powerful assumption reduces the complexity of nonequilibrium systems to the local application of well-founded equilibrium concepts. While this technique appears to be consistent for the description of some phenomena, we show that it fails for quantum friction by underestimating by approximately 80% the magnitude of the drag force. Our results show that the correlations among the components of driven, but steady-state, quantum systems invalidate the assumption of local thermal equilibrium, calling for a critical reexamination of this approach for describing the physics of nonequilibrium systems.

A full-body transcriptome and proteome resource for the European common carp.

BACKGROUND: The common carp (Cyprinus carpio) is the oldest, most domesticated and one of the most cultured fish species for food consumption. Besides its economic importance, the common carp is also highly suitable for comparative physiological and disease studies in combination with the animal model zebrafish (Danio rerio). They are genetically closely related but offer complementary benefits for fundamental research, with the large body mass of common carp presenting possibilities for obtaining sufficient cell material for advanced transcriptome and proteome studies. RESULTS: Here we have used 19 different tissues from an F1 hybrid strain of the common carp to perform transcriptome analyses using RNA-Seq. For a subset of the tissues we also have performed deep proteomic studies. As a reference, we updated the European common carp genome assembly using low coverage Pacific Biosciences sequencing to permit high-quality gene annotation. These annotated gene lists were linked to zebrafish homologs, enabling direct comparisons with published datasets. Using clustering, we have identified sets of genes that are potential selective markers for various types of tissues. In addition, we provide a script for a schematic anatomical viewer for visualizing organ-specific expression data. CONCLUSIONS: The identified transcriptome and proteome data for carp tissues represent a useful resource for further translational studies of tissue-specific markers for this economically important fish species that can lead to new markers for organ development. The similarity to zebrafish expression patterns confirms the value of common carp as a resource for studying tissue-specific expression in cyprinid fish. The availability of the annotated gene set of common carp will enable further research with both applied and fundamental purposes.

Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.

Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings.

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.

Targeting oncogene expression to endothelial cells induces proliferation of the myelo-erythroid lineage by repressing the Notch pathway.

Human oncogenes involved in the development of hematological malignancies have been widely used to model experimental leukemia. However, models of myeloid leukemia rarely reproduce the human disease in full, due to genetic complexity or to difficulties in targeting leukemia initiating cells. Here, we used a zebrafish genetic model to induce the expression of oncogenic RAS in endothelial cells, including the hemogenic endothelium of the dorsal aorta that generates hematopoietic cells, and observed the development of a myelo-erythroid proliferative disorder. In larvae, the phenotype is characterized by disruption of the vascular system and prominent expansion of the caudal hematopoietic tissue. In few surviving juveniles, increased number of immature hematopoietic cells and arrest of myeloid maturation was found in kidney marrow. Peripheral blood showed increased erythroblasts and myeloid progenitors. We found that the abnormal phenotype is associated with a downregulation of the Notch pathway, whereas overexpressing an activated form of Notch together with the oncogene prevents the expansion of the myelo-erythroid compartment. This study identifies the downregulation of the Notch pathway following an oncogenic event in the hemogenic endothelium as an important step in the pathogenesis of myelo-erythroid disorders and describes a number of potential effectors of this transformation.

Robust constraint on a drifting proton-to-electron mass ratio at z=0.89 from methanol observation at three radio telescopes.

A limit on a possible cosmological variation of the proton-to-electron mass ratio µ is derived from methanol (CH3OH) absorption lines in the benchmark PKS1830-211 lensing galaxy at redshift z=0.89 observed with the Effelsberg 100-m radio telescope, the Institute de Radio Astronomie Millimétrique 30-m telescope, and the Atacama Large Millimeter/submillimeter Array. Ten different absorption lines of CH3OH covering a wide range of sensitivity coefficients K(µ) are used to derive a purely statistical 1σ constraint of Δµ/µ=(1.5±1.5)×10(-7) for a lookback time of 7.5 billion years. Systematic effects of chemical segregation, excitation temperature, frequency dependence, and time variability of the background source are quantified. A multidimensional linear regression analysis leads to a robust constraint of Δµ/µ=(-1.0±0.8(stat)±1.0(sys))×10(-7).

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

Schottky barrier SOI-MOSFETs with high-k La(2)O(3)/ZrO(2) gate dielectrics.

Schottky barrier SOI-MOSFETs incorporating a La(2)O(3)/ZrO(2) high-k dielectric stack deposited by atomic layer deposition are investigated. As the La precursor tris(N,N'-diisopropylformamidinato) lanthanum is used. As a mid-gap metal gate electrode TiN capped with W is applied. Processing parameters are optimized to issue a minimal overall thermal budget and an improved device performance. As a result, the overall thermal load was kept as low as 350, 400 or 500 °C. Excellent drive current properties, low interface trap densities of 1.9 × 10(11) eV(-1) cm(-2), a low subthreshold slope of 70-80 mV/decade, and an I(ON)/I(OFF) current ratio greater than 2 × 10(6) are obtained.

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta.

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

Tuning the electrical performance of Ge nanowire MOSFETs by focused ion beam implantation.

In this work, we demonstrate an approach to tune the electrical behavior of our Ω-gated germanium-nanowire (Ge-NW) MOSFETs by focused ion beam (FIB) implantation. For the MOSFETs, 35 nm thick Ge-NWs are covered by atomic layer deposition (ALD) of a high-κ gate dielectric. With the Ω-shaped metal gate acting as implantation mask, highly doped source/drain (S/D) contacts are formed in a self-aligned process by FIB implantation. Notably, without any dopant activation by annealing, the devices exhibit more than three orders of magnitude higher I(ON) currents, an improved I(ON)/I(OFF) ratio, a higher mobility and a reduced subthreshold slope of 140 mV/decade compared to identical Ge-NW MOSFETs without FIB implantation.

[Current knowledge in molecular pathology of urothelial cancer]. / Stand des Wissens zur molekularen Pathologie des Urothelkarzinoms.

Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.

Extraendothelial and constitutive COX-2 expression is involved in the contractile effect of angiotensin II in the rat aorta.

1 The role of the extraendothelial and constitutive isoforms of cyclo-oxygenase-2 (COX-2) in the contractile effect of angiotensin II (Ang II) was investigated using thoracic and abdominal aortic rings without endothelium from young Wistar rats. 2 Ang II elicited similar contractions in both aortic segments, and the effect was inhibited by pretreatment with NS398 (a selective COX-2 inhibitor) but not SC-560 [selective cyclo-oxygenase-1 (COX-1) inhibitor]. 3 COX-2 mRNA was expressed under basal conditions in both aortic segments. Additionally, Ang II increased COX-2 mRNA expression in the abdominal but not the thoracic segment, while cycloheximide (a protein synthesis inhibitor) did not affect the contractile response to Ang II in either of the two segments; this suggests that the effect is not associated with de novo COX-2 synthesis. 4 In conclusion, the basal amount of COX-2 found in aortic smooth muscle cells is sufficient to explain the production of the prostanoids related to the contractile effect of Ang II. The production of these prostanoids, which are derived from constitutive COX-2, occurs independently of the endothelium vascular system.

Scalable approach for vertical device integration of epitaxial nanowires.

In this letter, we demonstrate the simultaneous vertical integration of self-contacting and highly oriented nanowires (NWs) into airbridge structures, which have been developed into surround gated metal oxide semiconductor field effect transistors (MOSFETs). With the use of conventional photolithography, reactive ion etching (RIE), and low pressure chemical vapor deposition, a suspended vertical NW architecture is formed on a silicon on insulator (SOI) substrate where the nanodevice will later be fabricated on. The vapor-liquid-solid (VLS) grown Si-NWs are contacted to prepatterned airbridges by a self-aligned process, and there is no need for postgrowth NW assembly or alignment. Such vertical NW architecture can be easily integrated into existing ICs processes opening the path to a new generation of nonconventional nano devices. To demonstrate the potential of this method, surround gated vertical MOSFETs have been fabricated with a highly simplified integration scheme combining top-down and bottom-up approaches, but in the same way, one can think about the realization of integrated nano sensors on the industrial scale.

Bilateral cochlear ablation in postnatal rat disrupts development of banded pattern of projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus.

Axonal projections from the dorsal nucleus of the lateral lemniscus (DNLL) distribute contralaterally in a pattern of banded layers in the central nucleus of the inferior colliculus (IC). The banded pattern of DNLL projections is already in the IC by onset of hearing in postnatal rat pups. Previously, it was shown that unilateral cochlear ablation in neonatal rat pups disrupted the banded pattern in IC for the projections of the DNLL contralateral to the ablation but not those of the DNLL ipsilateral to the ablation. In the present study, bilateral cochlear ablation or sham surgery was performed at postnatal day 9 (P9) after which rat pups were killed at P12 and the brains removed to study axonal projections of the DNLL. A lipophilic carbocyanine dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), was placed in the dorsal tegmental commissure of Probst to label decussating DNLL axons that end in the central nucleus of the contralateral IC. The distribution of labeled fibers across the central nucleus of the IC was analyzed in digital images by comparing the pattern of labeling with a sine model of periodic distribution of banded layers. In the control group, labeled axons formed a regular pattern of dense banded layers in IC. In the bilateral cochlear ablation group, labeled axons in the IC were distributed diffusely and there was little or no regular pattern of dense bands of axonal labeling. The influence of the cochlea on developing auditory circuits possibly mediated by activity-dependent mechanisms is discussed.

Evidence of alpha1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease.

1 Alpha1-Adrenoceptor (alpha1-AR) subtypes were characterized in isolated omental arteries obtained after abdominal surgery in patients with end-stage renal disease (ESRD) or with Diabetes Mellitus type 2 plus ESRD (ESRD-DM). 2 Omental arteries from patients with ESRD and ESRD-DM elicited a significant increase in sensitivity to phenylephrine with a pD(2) (-log EC50) of 6.7 and 6.6, respectively, vs. the control (5.8, P < 0.001). 3 Stimulation with phenylephrine was conducted in the presence or absence of selective alpha1-AR competitive antagonists: 5-methylurapidil (alpha1A-), AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol; alpha1B-) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4.5] decane-7,9-dione; alpha(1D)-). The relative abundance of mRNA for all three alpha(1)-ARs was determined. 4 The maximal contractile responses to phenylephrine were: E(max) 1.59 +/- 0.17, 1.48 +/- 0.08 and 1.55 +/- 0.14 g for the ESRD, ESRD-DM and control groups, respectively. 5 Functionally, there was an increment in the affinity for the alpha(1A)-AR antagonist (pA2: control 7.45, ESRD 8.36, ESRD-DM 8.0; P < 0.01), and a reduction in the alpha1B-AR antagonist affinity (8.3 for controls, 7.6 for ESRD and 7.3 for ESRD-DM; P < 0.01) associated with renal disease. The affinities for the alpha1D-AR antagonist were similar among the studied groups (8.5 for the controls, 8.7 for the ESRD and 8.1 for the ESRD-DM groups). 6 Renal disease increased mRNA expression of alpha(1B)-ARs and reduced both alpha1A- and alpha(1D)-ARs subtypes in ESRD and ESRD-DM patients. 7 The results suggest that human omental arteries exposed to chronic uraemia show vascular hypersensitivity to phenylephrine, because of functional alpha1-AR changes.

Cochlear ablation in adult ferrets results in changes in insulin-like growth factor-1 and synaptophysin immunostaining in the cochlear nucleus.

Afferent activity modulates synaptic plasticity as well as the levels of activity-dependent molecules such as growth factors. Disruption of this activity due to deafferentation has been shown to result in an altered trophic support and consequently in changes in neuronal excitability and synaptic transmission. In the present study, to test whether lack of cochlear integrity results in changes in insulin-growth factor-1 (IGF-1) and synaptophysin immunostaining in the cochlear nucleus, the first relay structure in the auditory pathway, unilateral cochlear ablations were performed in adult ferrets. Changes in IGF-1 and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN) and dorsal cochlear nucleus (DCN) at 1, 20 and 90 days after deafferentation. An increase in IGF-1 immunostaining within AVCN, PVCN and DCN was observed ipsilaterally at all survival times after cochlear ablation when compared with the contralateral side and unoperated animals. This increase was accompanied by a significant ipsilateral increase in the mean gray level of synaptophysin immunostaining as well as a decrease in the area of synaptophysin immunostaining at 1 and 20 days after the ablation in AVCN, PVCN and DCN compared with the contralateral side and control animals. These changes in synaptophysin immunostaining were no longer present 90 days after cochlear ablation. The present results provide evidence of a persistent upregulation in IGF-1 and a transitory upregulation in synaptophysin levels in the cochlear nucleus that may reflect neuroprotective mechanisms following the loss of trophic support from spiral ganglion neurons.

MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells.

Matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are involved in colon cancer progression and metastasis due to their ability to degrade extracellular matrix (ECM) components. In previous studies we described the MMP-9 hemopexin like domain (MMP-9-PEX) as an MMP-9 antagonist. In the present study it was examined whether recombinant MMP-9-PEX has an inhibitory effect on migration and adhesion of colorectal carcinoma cells. Furthermore, we searched for MMP-9 substrate binding sites within the MMP-9-PEX by surface plasmon resonance. Migration of SW620 and LS174 cells was investigated in a modified Boyden chamber assay. In the presence of 0.2 microg/ml MMP-9-PEX migration of SW620 was decreased by 34%, while addition of 0.4 microg/ml diminished migration by 56%. Migration of LS174 cells was not affected by MMP-9-PEX. Adhesion studies were performed on 96-well plates coated with gelatin, collagen type I, and laminin, respectively. In the presence of MMP-9-PEX, adhesion of SW620 cells to these coating substrates was significantly inhibited. Surface plasmon resonance studies revealed binding of collagen type I and IV, elastin, and fibrinogen to proMMP-9 as well as to MMP-9-PEX. However, equilibrium constants (Kd) indicated a higher affinity of proMMP-9 to the matrix proteins. This could indicate that there is more than one binding site for matrix components within the entire proMMP-9 molecule. Since migration and adhesion of metastatic colorectal carcinoma cells were reduced by MMP-9-PEX, this recombinant MMP-9 antagonist might be of therapeutical interest.