Dynamic Nanoindentation and Short-Range Order in Equiatomic NiCoCr Medium-Entropy Alloy Lead to Novel Density Wave Ordering.

Chemical short-range order is believed to be a key contributor to the exceptional properties of multicomponent alloys. However, its direct validation and confirmation has been highly elusive in most compounds. Recent studies for equiatomic NiCoCr alloys have shown that thermal treatments (i.e., annealing and aging) may facilitate and manipulate such ordering. In this work, by using molecular simulations, we show that nanomechanical probes, such as nanoindentation, may be utilized toward further manipulation of chemical short-range order, providing explicit validation pathways. By using well established interatomic potentials, we perform hybrid molecular-dynamics-Monte Carlo at room temperature to demonstrate that particular dwell nanoindentation protocols can lead, through thermal Monte Carlo equilibration, to local reorganization under the indenter tip, toward a density-wave stripe pattern. We characterize the novel density-wave structures, which are highly anisotropic and dependent on local, nanoindentation-induced stress concentrations, and we show how they deeply originate from intrinsic features of interelemental interactions. Furthermore, we show that these novel patterns consistently scale with the incipient plastic zone, under the indenter tip, justifying their observation at experimentally feasible nanoindentation depths.

Isolation, identification and screening of yeasts towards their ability to assimilate biodiesel-derived crude glycerol: microbial production of polyols, endopolysaccharides and lipid.

AIMS: To assess the ability of various newly isolated or belonging in official collections yeast strains to convert biodiesel-derived glycerol (Gly) into added-value compounds. METHODS AND RESULTS: Ten newly isolated yeast strains belonging to Debaryomyces sp., Naganishia uzbekistanensis, Rhodotorula sp. and Yarrowia lipolytica, isolated from fishes, metabolized Gly under nitrogen limitation. The aim of the study was to identify potential newly isolated microbial candidates that could produce single-cell oil (SCO), endopolysaccharides and polyols when these micro-organisms were grown on biodiesel-derived Gly. As controls producing SCO and endopolysaccharides were the strains Rhodotorula glutinis NRRL YB-252 and Cryptococcus curvatus NRRL Y-1511. At initial Gly (Gly0 ) ≈40 g l-1 , most strains presented remarkable dry cell weight (DCW) production, whereas Y. lipolytica and Debaryomyces sp. produced non-negligible quantities of mannitol and arabitol (Ara). Five strains were further cultivated at increasing Gly0 concentrations. Rhodotorula glutinis NRRL YB-252 produced 7·2 g l-1 of lipid (lipid in DCW value ≈38% w/w), whereas Debaryomyces sp. FMCC Y69 in batch-bioreactor experiment with Gly0 ≈80 g l-1 , produced 30-33 g l-1 of DCW and ~30 g l-1 of Ara. At shake-flasks with Gly0 ≈125 g l-1 , Ara of ~48 g l-1 (conversion yield of polyol on Gly consumed ≈0·62 g g-1 ) was achieved. Cellular lipids of all yeasts contained in variable concentrations oleic, palmitic, stearic and linoleic acids. CONCLUSIONS: Newly isolated, food-derived and non-previously studied yeast isolates converted biodiesel-derived Gly into several added-value metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: Alternative ways of crude Gly valorization through yeast fermentations were provided and added-value compounds were synthesized.

Production of oils and fats by oleaginous microorganisms with an emphasis given to the potential of the nonconventional yeast Yarrowia lipolytica.

Recently, there has been a great upsurge of interest in studies related to several aspects of microbial lipid production, which is one of the top topics in relevant research fields due to the high demand of these fatty materials in food, medical, oleochemical and biofuel industries. Lipid accumulation by the so-called "oleaginous microorganisms" can generate more than 20% w/w of oil in dry biomass and is governed by a plethora of parameters, such as medium pH, incubation temperature, nutrient limitation and C/N (carbon/nitrogen) ratio, which drastically affect the lipid production bioprocess. Until now, considerable work has been undertaken to find the cheapest substrate to enable lipid fermentation by oleaginous microorganisms. This review principally details information regarding microbial lipids, suitable production conditions and focuses attention on using the yeast Yarrowia lipolytica to achieve these objectives. Lipid production by this yeast is discussed and the necessary conditions and suitable substrates are reviewed.

Lipids from yeasts and fungi: physiology, production and analytical considerations.

The last years there has been a significant rise in the number of publications in the international literature that deal with the production of lipids by microbial sources (the 'single cell oils; SCOs' that are produced by the so-called 'oleaginous' micro-organisms). In the first part of the present review article, a general overview of the oleaginous micro-organisms (mostly yeasts, algae and fungi) and their potential upon the production of SCOs is presented. Thereafter, physiological and kinetic events related with the production of, mostly, yeast and fungal lipids when sugars and related substrates like polysaccharides, glycerol, etc. (the de novo lipid accumulation process) or hydrophobic substrates like oils and fats (the ex novo lipid accumulation process) were employed as microbial carbon sources, are presented and critically discussed. Considerations related with the degradation of storage lipid that had been previously accumulated inside the cells, are also presented. The interplay of the synthesis of yeast and fungal lipids with other intracellular (i.e. endopolysaccharides) or extracellular (i.e. citric acid) secondary metabolites synthesized is also presented. Finally, aspects related with the lipid extraction and lipidome analysis of the oleaginous micro-organisms are presented and critically discussed.

Lipid production and characterization by Mortierella (Umbelopsis) isabellina cultivated on lignocellulosic sugars.

AIMS: To study and characterize the lipids produced by Mortierella (Umbelopsis) isabellina, during its growth on mixtures of glucose and xylose. METHODS AND RESULTS: Glucose and xylose were utilized as carbon sources, solely or in blends, under nitrogen-limited conditions, in batch-flask trials (initial sugars at 80 g l-1 ). Significant lipid production (maximum lipid 17·8 g l-1 ; lipid in DCW 61·0% w/w; lipid on glucose consumed 0·23 g g-1 ) occurred on glucose employed solely, while xylose concentration in the growth medium was conversely correlated with lipid accumulation. With increasing xylose concentrations into the blend, lipid storage decreased while xylitol in significant concentrations (up to 24 g l-1 ) was produced. Irrespective of the sugar blend employed, significant quantities of endopolysaccharides were detected in the first growth steps (in the presence of nitrogen into the medium or barely after its disappearance) while lipids were stored thereafter. Neutral lipids, mainly composed of triacylglycerols, were the main microbial lipid fraction. Phospholipids were quantified both through fractionation and subsequent gravimetric determination and also through determination of phosphorus, and it seemed that the second method was more accurate. Phospholipids were mainly composed of phosphatidylcholine and another nonidentified compound presumably being phosphatidyldimethylethanolamine. CONCLUSIONS: Mortierella isabellina is suitable to convert lignocellulosic sugars into lipids. SIGNIFICANCE AND IMPACT OF THE STUDY: Differentiations between metabolism on xylose and glucose were reported. Moreover, this is one of the first reports indicating extensive analysis of microbial lipids produced by M. isabellina.

Lipid production by yeasts growing on biodiesel-derived crude glycerol: strain selection and impact of substrate concentration on the fermentation efficiency.

AIMS: To screen yeasts in relation to the potential to produce single cell oil (SCO) from biodiesel-derived glycerol and to enhance SCO production in Lipomyces starkeyi and Rhodosporidium toruloides yeasts. METHODS AND RESULTS: Yarrowia lipolytica, Cryptococcus curvatus, R. toruloides and L. starkeyi were grown in nitrogen-limited flask cultures. Yarrowia lipolytica strains produced citric acid and mannitol. Lipomyces starkeyi DSM 70296 and R. toruloides NRRL Y-27012 showed potential for SCO production, and were cultivated at increasing the initial glycerol concentrations with the initial nitrogen concentration remaining constant. Significant biomass and SCO production were reported even in cultures with high initial glycerol concentrations (i.e. 180 g l(-1) ). Lipid quantities of c. 12 g l(-1) (lipid in dry cell weight 35-40%) were obtained for both L. starkeyi and R. toruloides, quite high values compared with literature values for oleaginous micro-organisms growing on glycerol. However, these strains exhibited different kinetic profiles in the synthesis of intracellular polysaccharides. Lipomyces starkeyi produced a significant quantity of polysaccharides (c. 7 g l(-1) ). The yeast lipids contained mainly oleic and palmitic and to a lesser extent linoleic and stearic acids. CONCLUSIONS: Lipomyces starkeyi and R. toruloides are potential SCO producers from crude glycerol. SIGNIFICANCE AND IMPACT OF THE STUDY: Very scarce numbers of reports have indicated the production of SCO by L. starkeyi and R. toruloides growing on glycerol. We report here that these yeasts are able efficiently to convert raw glycerol into SCO, while L. starkeyi also synthesizes intracellular polysaccharides in marked quantities.

Evaluating glucose and xylose as cosubstrates for lipid accumulation and γ-linolenic acid biosynthesis of Thamnidium elegans.

AIMS: To study the biotechnological production of lipids containing rich amounts of the medically and nutritionally important γ-linolenic acid (GLA), during cultivation of the Zygomycetes Thamnidium elegans, on mixtures of glucose and xylose, abundant sugars of lignocellulosic biomass. METHODS AND RESULTS: Glucose and xylose were utilized as carbon sources, solely or in mixtures, under nitrogen-limited conditions, in batch-flask or bioreactor cultures. On glucose, T. elegans produced 31.9 g l(-1) of biomass containing 15.0 g l(-1) lipid with significantly high GLA content (1014 mg l(-1)). Xylose was proved to be an adequate substrate for growth and lipid production. Additionally, xylitol secretion occurred when xylose was utilized as carbon source, solely or in mixtures with glucose. Batch-bioreactor trials on glucose yielded satisfactory lipid production, with rapid substrate consumption rates. Analysis of intracellular lipids showed that the highest GLA content was observed in early stationary growth phase, while the phospholipid fraction was the most unsaturated fraction of T. elegans. CONCLUSIONS: Thamnidium elegans represents a promising fungus for the successful valorization of sugar-based lignocellulosic residues into microbial lipids of high nutritional and pharmaceutical interest. SIGNIFICANCE AND IMPACT OF THE STUDY: Xylitol production and cultivation in bioreactor trials is reported for the first time for T. elegans, while cultivation on xylose-based media resulted in high GLA production by this fungus.

Machine learning dislocation density correlations and solute effects in Mg-based alloys.

Magnesium alloys, among the lightest structural materials, represent excellent candidates for lightweight applications. However, industrial applications remain limited due to relatively low strength and ductility. Solid solution alloying has been shown to enhance Mg ductility and formability at relatively low concentrations. Zn solutes are significantly cost effective and common. However, the intrinsic mechanisms by which the addition of solutes leads to ductility improvement remain controversial. Here, by using a high throughput analysis of intragranular characteristics through data science approaches, we study the evolution of dislocation density in polycrystalline Mg and also, Mg-Zn alloys. We apply machine learning techniques in comparing electron back-scatter diffraction (EBSD) images of the samples before/after alloying and before/after deformation to extract the strain history of individual grains, and to predict the dislocation density level after alloying and after deformation. Our results are promising given that moderate predictions (coefficient of determination [Formula: see text] ranging from 0.25 to 0.32) are achieved already with a relatively small dataset ([Formula: see text] 5000 sub-millimeter grains).

Biotechnological conversion of waste cooking olive oil into lipid-rich biomass using Aspergillus and Penicillium strains.

AIMS: In this study, we have investigated the biochemical behaviour of Aspergillus sp. (five strains) and Penicillium expansum (one strain) fungi cultivated on waste cooking olive oil. The production of lipid-rich biomass was the main target of the work. In parallel, the biosynthesis of other extracellular metabolites (organic acids) and enzyme (lipase) and the substrate fatty acid specificity of the strains were studied. METHODS AND RESULTS: Carbon-limited cultures were performed on waste oil, added in the growth medium at 15g l(-1) , and high biomass quantities were produced (up to c.18g l(-1) , conversion yield of c. 1·0 g of dry biomass formed per g of fat consumed or higher). Cellular lipids were accumulated in notable quantities in almost all cultures. Aspergillus sp. ATHUM 3482 accumulated lipid up to 64·0% (w/w) in dry fungal mass. In parallel, extracellular lipase activity was quantified, and it was revealed to be strain and fermentation time dependent, with a maximum quantity of 645 U ml(-1) being obtained by Aspergillus niger NRRL 363. Storage lipid content significantly decreased at the stationary growth phase. Some differences in the fatty acid composition of both cellular and residual lipids when compared with the initial substrate fat used were observed; in various cases, cellular lipids more saturated and enriched with arachidic acid were produced. Aspergillus strains produced oxalic acid up to 5·0 g l(-1) . CONCLUSIONS: Aspergillus and Penicillium strains are able to convert waste cooking olive oil into high-added-value products. SIGNIFICANCE AND IMPACT OF THE STUDY: Increasing fatty wastes amounts are annually produced. The current study provided an alternative way of biovalourization of these materials, by using them as substrates, to produce added-value compounds.

Organic nitrogen of tomato waste hydrolysate enhances glucose uptake and lipid accumulation in Cunninghamella echinulata.

AIMS: To investigate the effect of organic nitrogen on lipogenesis during growth of Cunninghamella echinulata on tomato waste hydrolysate (TWH) media. METHODS AND RESULTS: Cunninghamella echinulata grown on a TWH medium rapidly took up glucose and produced large amounts of lipids. However, when some quantities of the organic nitrogen were removed from TWH (by acid followed by alkaline precipitation of proteins) the uptake of glucose was dramatically reduced and large quantities of fungal biomass having low lipid content were produced. Nevertheless, when glycerol was used as carbon source instead of glucose, the uptake rate as well as the biomass production and the lipid accumulation processes were unaffected by the TWH organic nitrogen removal. Finally, when the fungus was grown on a glucose supplemented TWH medium that contained no assimilable organic nitrogen (after further precipitation of proteins with methanol), the produced biomass contained non-negligible quantities of lipids, although glucose uptake remained low. Lipid analysis showed that the produced lipids comprised mainly of neutral lipids, which were preferentially consumed during lipid turnover. Lipid production on the original TWH medium having glucose as carbon source was 0.48 g of lipid per gram of dry biomass, corresponding to 8.7 g of lipid per litre of growth medium. The produced lipids contained 11.7%gamma-linolenic acid (GLA), hence the GLA yield was more than 1 g l(-1). CONCLUSIONS: Organic nitrogen compounds found in TWH favour glucose (but not glycerol) uptake and lipid accumulation in C. echinulata. SIGNIFICANCE AND IMPACT OF THE STUDY: Agro-industrial wastes containing organic nitrogen, such as tomato waste, are produced in vast amounts causing severe environmental problems. These wastes could be used as fermentation feedstock to produce microbial lipids.

Laning and clustering transitions in driven binary active matter systems.

It is well known that a binary system of nonactive disks that experience driving in opposite directions exhibits jammed, phase separated, disordered, and laning states. In active matter systems, such as a crowd of pedestrians, driving in opposite directions is common and relevant, especially in conditions which are characterized by high pedestrian density and emergency. In such cases, the transition from laning to disordered states may be associated with the onset of a panic state. We simulate a laning system containing active disks that obey run-and-tumble dynamics, and we measure the drift mobility and structure as a function of run length, disk density, and drift force. The activity of each disk can be quantified based on the correlation timescale of the velocity vector. We find that in some cases, increasing the activity can increase the system mobility by breaking up jammed configurations; however, an activity level that is too high can reduce the mobility by increasing the probability of disk-disk collisions. In the laning state, the increase of activity induces a sharp transition to a disordered strongly fluctuating state with reduced mobility. We identify a novel drive-induced clustered laning state that remains stable even at densities below the activity-induced clustering transition of the undriven system. We map out the dynamic phase diagrams highlighting transitions between the different phases as a function of activity, drive, and density.

Biorefining of by-product streams from sunflower-based biodiesel production plants for integrated synthesis of microbial oil and value-added co-products.

This study focuses on the valorisation of crude glycerol and sunflower meal (SFM) from conventional biodiesel production plants for the separation of value-added co-products (antioxidant-rich extracts and protein isolate) and for enhancing biodiesel production through microbial oil synthesis. Microbial oil production was evaluated using three oleaginous yeast strains (Rhodosporidium toruloides, Lipomyces starkeyi and Cryptococcus curvatus) cultivated on crude glycerol and nutrient-rich hydrolysates derived from either whole SFM or SFM fractions that remained after separation of value-added co-products. Fed-batch bioreactor cultures with R. toruloides led to the production of 37.4gL(-1) of total dry weight with a microbial oil content of 51.3% (ww(-1)) when a biorefinery concept based on SFM fractionation was employed. The estimated biodiesel properties conformed with the limits set by the EN 14214 and ASTM D 6751 standards. The estimated cold filter plugging point (7.3-8.6°C) of the lipids produced by R. toruloides is closer to that of biodiesel derived from palm oil.

High production of 1,3-propanediol from industrial glycerol by a newly isolated Clostridium butyricum strain.

Batch and continuous cultures of a newly isolated Clostridium butyricum strain were carried out on industrial glycerol, the major by-product of the bio-diesel production process. For both types of cultures, the conversion yield obtained was around 0.55 g of 1,3-propanediol formed per 1 g of glycerol consumed whereas the highest 1,3-propanediol concentration, achieved during the single-stage continuous cultures was 35-48 g l-1. Moreover, the strain presented a strong tolerance at the inhibitory effect of the 1,3-propanediol, even at high concentrations of this substance at the chemostat (e.g. 80 g l-1). 1,3-Propanediol was associated with cell growth whereas acetate and butyrate seemed non growth-associated products. At low and medium dilution rates (until 0.1 h-1), butyrate production was favoured, whereas at higher rates acetate production increased. The maximum 1,3-propanediol volumetric productivity obtained was 5.5 g l-1 h-1. A two-stage continuous fermentation was also carried out. The first stage presented high 1,3-propanediol volumetric productivity, whereas the second stage (with a lower dilution rate) served to further increase the final product concentration. High 1,3-propanediol concentrations were achieved (41-46 g l-1), with a maximum volumetric productivity of 3.4 g l-1 h-1. A cell concentration decrease was reported between the second and the first fermentor.

Ambulatory blood pressure monitoring in normotensive pregnant women.

Ambulatory blood pressure monitoring (ABPM) provides a profile of blood pressure (BP) during daily activities and sleep and could uncover the inter-individual variability of BP. The aims of this study were to establish the normal values of the ABPM during the three trimesters of normal pregnancy, and to compare these values with those obtained in the office. ABPM was carried out on 22 normotensive pregnant women. BP values were compared with those obtained in the office. BP during the third trimester was significantly higher than the BP recorded during the first two gestational periods. In the three trimesters of pregnancy mean ambulatory systolic and diastolic BP were lower than the BP measured in the office in lying and standing positions. On the other hand, mean ambulatory BP (systolic and diastolic) measured during daily activities was not significantly different from the BP measured in the office. Sleeping BP was significantly lower than waking values in all trimesters, while there were not significant differences in the degree of BP fall among the three trimesters. Six women were sequentially studied during the three trimesters of pregnancy and particularly at the 12, 24 and 32 weeks of pregnancy. In these women, a small but significant rise in mean 24 h systolic and diastolic BP was observed at 32 weeks of pregnancy. Sleeping BP was significantly lower than waking values in the three trimesters. No significant difference in the degree of BP fall on the three gestational dates was found. It is concluded that ABPM is a useful tool for the evaluation of BP variability during pregnancy. During normal pregnancy ambulatory BP levels are highest in the day and lowest at night at all gestational ages and increased at the third trimester of pregnancy compared to the values observed during the first two gestational periods.

Aberrant E-cadherin expression associated with loss of differentiation and advanced stage in human pancreatic cancer.

E-cadherin is a cell-cell adhesion molecule involved in tumour invasion and metastasis. We evaluated E-cadherin expression immunohistochemically in 43 formalin-fixed, paraffin-embedded specimens of pancreatic cancer and investigated its relationship to histopathological features. In non-cancerous pancreatic cells E-cadherin immunoreactivity was localized at the cell membrane, particularly at the intercellular junctions. Abnormal E-cadherin expression was found in 18 (42%) cases. A significantly higher proportion of poorly-differentiated tumours (71%) showed abnormal E-cadherin expression compared with moderately (50%) and well (19%) differentiated tumours (P = 0.037). There was a significant correlation between abnormal E-cadherin expression and lymph node involvement (P = 0.013), the presence of distant metastases (P = 0.034) and advanced tumour stage (P = 0.025). These findings suggest that loss of normal E-cadherin expression is involved in the progression of pancreatic cancer.

Phenolic removal in a model olive oil mill wastewater using Pleurotus ostreatus in bioreactor cultures and biological evaluation of the process.

Pleurotus ostreatus grown in bioreactor batch cultures in a model phenolic wastewater (diluted and sterilized olive oil mill wastewater-OMW), caused significant phenolic removal. Laccase, the sole ligninolytic enzyme detected in the growth environment, was produced during primary metabolic growth. The bioprocess was simulated with the aid of a mathematical model and the parameters of growth were determined. When the fungal biomass was increased in the reactor (during repeated batch experiments) the rate of reducing sugars consumption progressively increased, but a phenolic fraction seemed of being strongly resistant to oxidation. The toxicity of OMW against the seeds of Lepidium sativum and the marine Branchiopoda Artemia sp. was significantly decreased after biotreatment. On the contrary, the toxicity against the freshwater Branchiopoda Daphnia magna was not affected by the treatment, whereas on the soil and freshwater sediments Ostracoda Heterocypris incongruens was slightly decreased. Both treated and untreated OMWs, used as water for irrigation of lettuce and tomato plants, did not significantly affect the uptake of several nutrients by the cultivated plants, but resulted in a decrease in the plant yields, which was minimized when high OMW dilutions were used. As a conclusion, P. ostreatus is able to reduce phenolic content and toxicity of sterilized OMW, in bioreactor cultures. However, high OMW dilutions should be used, and/or additional treatment should be applied before use of the OMW in the environment, e.g. as water for irrigation. Further research should be done in order to transfer this technology under industrial conditions (e.g. by using unsterilized OMW).

Enzyme-catalyzed synthesis of alkyl-beta-glucosides in a water-alcohol two-phase system.

The enzymic synthesis of alkyl-beta-glucosides by water-immiscible alcohols was studied in stirred flasks as well as in a tubular enzymatic reactor. In the first case, direct alkylation of beta-D-glucose from hexanol using immobilized beta-glycosidase gave a higher conversion yield and final product concentration than that using the enzyme in its free state (yield 10 against 8% mol/mol, concentration 2 against 1.6 g/l). Direct glycosylation of beta-D-glucose from hexanol resulted in a higher reaction performance (yield 10%) than that from octanol (yield 5%). However, the two different incubation temperatures tested (37 degrees C and 50 degrees C), showed no significant differences concerning final product concentrations. The more interesting results were obtained by transglycosylation of methyl-1-beta-glucose from hexanol, with a conversion yield of 21% mol/mol (product amount 4 g/l). However, the transgalactosylation of lactose from hexanol, catalyzed by a fungal beta-galactosidase, showed only a feeble reactivity. The feasibility of enzymic alkylation was also tested in a tubular enzymatic reactor; hexyl-1-beta-glucoside was produced via direct glycosylation from hexanol catalyzed by free beta-glycosidase with a final concentration 1.3-2.3 g/l and a yield varying between 11% and 20% mol/mol.

E-cadherin expression as a differentiation marker in gastric cancer.

BACKGROUND/AIMS: E-cadherin is a cell-cell adhesion molecule involved in tumor progression and metastasis. We evaluated the E-cadherin expression pattern in gastric cancer and investigated its relationship to histopathological features. METHODOLOGY: The expression of E-cadherin was evaluated in 83 formalin-fixed, paraffin-embedded specimens of gastric cancer by immunohistochemistry. RESULTS: In benign gastric mucosa, E-cadherin was expressed uniformly at the cell membrane. Abnormal E-cadherin expression with loss of membranous localization was found in 55 (56%) cancer specimens. Aberrant E-cadherin expression was found more often in diffuse (96%) and mixed type tumors (91%) than in intestinal type tumors (47%) (p=0.0001). A significantly higher proportion of signet-ring (84%) and undifferentiated tumors (87%) showed abnormal E-cadherin expression compared with adenocarcinomas with glandular morphology (57%) (p=0.01). There was a significant correlation between abnormal E-cadherin expression and degree of differentiation (p=0.0001), local tumor extent (p=0.002), and the presence of lymph node metastases (p=0.04). CONCLUSIONS: Loss of normal E-cadherin expression may serve as a differentiation marker in gastric cancer.

E-cadherin expression correlates with tumor differentiation in colorectal cancer.

BACKGROUND/AIMS: Epithelial cadherin (E-cadherin) is the main cell-cell adhesion molecule in all epithelia. Aberrant expression of this molecule has been implicated in tumor invasion and metastasis. We evaluated E-cadherin expression and cellular localization in colorectal cancer and investigated its relationship to histopathological features. METHODOLOGY: The expression of E-cadherin was evaluated in 57 formalin-fixed, paraffin-embedded specimens of colorectal cancer by immunohistochemistry. RESULTS: In normal colonic mucosa, E-cadherin was expressed uniformly at the cell membrane. Abnormal E-cadherin expression and/or cellular distribution was found in 46% of tumors. There was a significant correlation between E-cadherin expression and tumor grade with a trend towards reduced E-cadherin expression as the tumor grade increased. The association between E-cadherin expression and tumor stage was not significant. CONCLUSIONS: Abnormal E-cadherin expression in colorectal cancer correlates with loss of differentiation.