Zebrafish pancreas as a model for development and disease.

The vertebrate pancreas is composed of acinar tissue that produces digestive enzymes, a ductal system for transporting those enzymes, and the endocrine islets which produce hormones critical for organism glucose homeostasis. Recent studies have highlighted similarities between zebrafish and mammals in organ development, and increasingly reveal that the regulation of metabolic homeostasis is highly conserved as well. Use of zebrafish as a model organism, with its ease of genetic manipulation, high fecundity, and ready access for imaging, has been highly productive for studies of islet cell development. We review the most recent progress in our understanding of how the later forming endocrine cells develop from duct-associated progenitors and new tools available for these studies. We also discuss current approaches and technological advances for addressing beta cell physiology, organism glucose homeostasis, and associated processes within zebrafish. Finally, we describe emerging methods being used to establish new zebrafish models of diabetes and related pathologies, to expand the use of this model organism to discover new therapies and to facilitate studies of disease pathology.

Computed tomography score and pulmonary function in infants with chronic lung disease of infancy.

Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed. We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group. CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4-33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function. CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.

Intragenomic rearrangement in TT viruses: a possible role in the pathogenesis of disease.

A role for the ubiquitous Torque teno (TT) viruses in the pathogenesis of disease has not been resolved. In vivo and in vitro intragenomic rearrangement of TT virus genomes has been demonstrated. Replication in cell culture of a subviral molecule (411 bp) occurs through oligomerisation of RNA transcripts. Although the functions of the respective TT viral genes, as well as the newly formed genes in the rearranged subviral molecules, are largely unknown, certain similarities to genes of plant viruses of the family Geminiviridae will be described. A degree of similarity to certain cellular genes poses the question as to a role of molecular mimicry in the pathogenesis of autoimmune disease and diabetes.

Genomic instability during Myc-induced lymphomagenesis in the bursa of Fabricius.

Retroviral vector-mediated overexpression of c-myc in embryonic bursal precursors induces multi-staged tumorigenesis beginning with preneoplastic-transformed follicles (TF) and progressing to clonal metastatic B-cell lymphomas. Using a 13K chicken cDNA microarray, specifically enriched for chicken immune system expressed sequence tagged (ESTs), we carried out array-based comparative genomic hybridization (array-CGH) and detected significant DNA copy number change at many loci on most or all chromosomes in both early TF and end-stage lymphomas. Formation of long palindromes, through breakage-fusion-bridge cycles, is thought to play an early role in gene amplification. Employing genome-wide analysis of palindrome formation (GAPF), we detected extensive palindrome formation in early TF and end-stage lymphomas. The population of loci showing amplification by array-CGH was enriched for palindromes detected by GAPF providing strong evidence for genetic instability early in Myc-induced tumorigenesis and further support for the role of palindromes in gene amplification. Comparing gene copy number change and RNA expression changes profiled on the same cDNA array, we detected very little consistent contribution of gene copy number change to RNA expression changes. Palindromic loci in TF and tumors, however, were expressed, many at high levels, suggesting an abundance of RNA species with long double-stranded segments generated during tumorigenesis.

Regulation of cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRalpha).

The cholesterol 7alpha-hydroxylase gene (CYP7A1) plays an important role in regulation of bile acid biosynthesis and cholesterol homeostasis. Oxysterol receptor, LXR, stimulates, whereas the bile acid receptor, FXR, inhibits CYP7A1 transcription. The goal of this study was to investigate the role of LXRalpha on the regulation of rat, human and hamster CYP7A1 transcription in its native promoter and cellular context. Cotransfection with LXRalpha and RXRalpha expression plasmids strongly stimulated rat CYP7A1/luciferase reporter activity in HepG2 cells and oxysterol was not required. However, LXRalpha had much less effect on hamster and no significant effect on human CYP7A1 promoter activity in HepG2 cells. In Chinese hamster ovary cells, cotransfection with LXRalpha stimulated reporter activity by less than 2-fold and addition of 22(R)-hydroxycholesterol caused a small but significant stimulation of rat, human and hamster CYP7A1 promoter activity. At least two direct repeats of AGGTCA-like sequences with 4-base spacing (DR4) and five-base spacing (DR5), in previously identified bile acid response elements of the rat CYP7A1 were able to bind LXRalpha/RXRalpha and confer LXRalpha stimulation. However, LXRalpha did not bind to the corresponding sequences of the human gene and bound weakly to hamster and mouse DR4 sequences. Therefore, rats and mice have the unusual capacity to convert cholesterol to bile acids by LXRalpha-mediated stimulation of CYP7A1 transcription, whereas other species do not respond to cholesterol and develop hypercholesterolemia on a diet high in cholesterol.

Fast geodesic active contours.

We use an unconditionally stable numerical scheme to implement a fast version of the geodesic active contour model. The proposed scheme is useful for object segmentation in images, like tracking moving objects in a sequence of images. The method is based on the Weickert-Romeney-Viergever (additive operator splitting) AOS scheme. It is applied at small regions, motivated by the Adalsteinsson-Sethian level set narrow band approach, and uses Sethian's (1996) fast marching method for re-initialization. Experimental results demonstrate the power of the new method for tracking in color movies.

Two lineage boundaries coordinate vertebrate apical ectodermal ridge formation.

Proximal-distal outgrowth of the vertebrate limb bud is regulated by the apical ectodermal ridge (AER), which forms at an invariant position along the dorsal-ventral (D/V) axis of the embryo. We have studied the genetic and cellular events that regulate AER formation in the mouse. In contrast to implications from previous studies in chick, we identified two distinct lineage boundaries in mouse ectoderm prior to limb bud outgrowth using a Cre/loxP-based fate-mapping approach and a novel retroviral cell-labeling technique. One border is transient and at the limit of expression of the ventral gene En1, which corresponds to the D/V midline of the AER, and the second border corresponds to the dorsal AER margin. Labeling of AER precursors using an inducible Cre showed that not all cells that initially express AER genes form the AER, indicating that signaling is required to maintain an AER phenotype. Misexpression of En1 at moderate levels specifically in the dorsal AER of transgenic mice was found to produce dorsally shifted AER fragments, whereas high levels of En1 abolished AER formation. In both cases, the dorsal gene Wnt7a was repressed in cells adjacent to the En1-expressing cells, demonstrating that signaling regulated by EN1 occurs across the D/V border. Finally, fate mapping of AER domains in these mutants showed that En1 plays a part in positioning and maintaining the two lineage borders.

Sodium monochloroacetate causes cytotoxic effects, an increased lactate and pyruvate level and induces ultra structural and cytoskeletal alterations in cultured kidney and liver epithelial cells.

1. Monochloroacetic acid (MCAA) and its sodium salt, sodium monochloroacetate (SMCA) are widely used in chemical industries as intermediates in the synthesis of carboxymethylcellulose, phenoxyacetic acid, thioglycolic acid, glycine, indigoid dyes and others. Moreover, MCAA has been found as a by-product of the chlorination disinfection of drinking water and as an environmental contaminant of the atmosphere from the photodechlorination reactions of chlorinated hydrocarbons. Little is known about the mode of action of both compounds on the cellular level. From cases of accidental poisoning of man it is known that MCAA accumulates in liver and kidney. 2. In this study, the cytotoxicity of SMCA on cultured liver (Chang liver cells) and kidney epithelial cells of the proximal tubule (Opossum kidney cells) was investigated and its effect on metabolism, ultrastructure and organization of cytoskeleton was examined. 3. Independent from the growth state of the cells (proliferating or quiescent), the results clearly show that SMCA causes a dose-dependent decrease in cell viability after an exposure period of 24 h. In all experiments, proliferating cells were more sensitive than quiescent and confluent cells. Liver cells were less sensitive against SMCA treatment than kidney epithelial cells. In contrast to liver cells, kidney cells exhibited a dose-dependent decrease in cell volume. The decrease in cell viability was accompanied by an increase of lactate and pyruvate concentrations released into the culture medium. In the case of Opossum kidney cells, lactate and pyruvate levels increased 5 - 6-fold, whereas in the case of Chang liver cells the increase was approximately twofold. While the ultrastructure of liver cells remained unaltered after drug treatment, kidney cells exhibited cytoplasmic vacuolization, membraneous disruption and especially mitochondrial alterations. In accordance with the changes in the ultrastructure of Opossum cells, was the reorganization of cytoskeletal elements with an increased stress fiber network at the basolateral surface as well as a partial depolymerization of microtubules and vimentin filaments. A cytoskeletal reorganization was not observed for Chang liver cells after SMCA treatment. 4. The results demonstrate that SMCA causes a dose-dependent cytotoxicity which is accompanied by metabolic, mitochondrial and cytoskeletal alterations in the cells.

[Insufficient ventilation as the etiology of illness perception in an elementary school]. / Mangelhafte Lüftung als Auslöser von Befindlichkeitsstörungen in einer Grundschule.

PURPOSE: Two years after renovation of the classrooms in a primary school (installation of insulated windows and closing of the ventilation shaft) pupils and teachers complained about offensive odours, irritation of the eyes and of the nose, complaints of the respiratory tract, headaches and disturbed mental concentration. The presented study determines the causes, suggests measures for help and checks their effectiveness by means of measurements. METHODS: Before starting our measurements, the air quality had already been assessed by an expert. There was no evidence of elevated concentrations of air contaminants. Because of the content of phthalate plasticizers and flame retardants in the linoleum sealants there was an offensive odour. To determine the cause, the air in the subjective mostly affected classroom was analysed for phthalate plasticizers, their metabolites and alkyl phosphates. We also made aerosol measurements with a cascade impactor, determined bacterial counts in the air, and measured the indoor climate and the internal air flow. RESULTS: The concentrations of phthalate plasticizers and their metabolites in the air were not elevated significantly. The screening for alkyl phosphates was negative. The amount of inhalable particles was 0.046 mg/m3. The bacterial count in the air was negligible. On the other hand the indoor climate during the heating period in winter was remarkably changed. The average room temperature was 26 degrees C (reaching a maximum of 36 degrees C with direct sunlight in the classroom), the average humidity was 21% (minimum 7%) and the change of air was approximately 0.5 per hour. Reopening the ventilation shaft and tilting of only one window resulted in a much greater rate of air change. After installation of temperature regulators and regular use of the venetian blinds in the classroom, the room temperature and the relative humidity during the morning lessons were, as a rule, normalised. Among both pupils and teachers the reports of offensive odours and health disorders were subsequently clearly reduced. CONCLUSIONS: To determine the cause of health disorders indoors, it is apparently to be of great importance to carry out measurements of the climate as well as to assess the level of air contaminants. By use of modern energy-saving construction possible effects on the indoor climate should be be taken into account during the planning stage of changes to avoid health disorders resulting from changed interior climate conditions.

Farnesoid X receptor responds to bile acids and represses cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription.

Cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription is repressed by bile acids. The goal of this study is to elucidate the mechanism of CYP7A1 transcription by bile acid-activated farnesoid X receptor (FXR) in its native promoter and cellular context and to identify FXR response elements in the gene. In Chinese hamster ovary cells transfected with retinoid X receptor alpha (RXRalpha)/FXR, only chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were able to stimulate a heterologous promoter/reporter containing an ecdysone response element. In HepG2 cells, all bile acids (25 microM) were able to repress CYP7A1/luciferase reporter activity, and only CDCA and DCA further repressed reporter activity when cotransfected with RXRalpha/FXR. The concentration of CDCA required to inhibit 50% of reporter activity (IC(50)) was determined to be approximately 25 microM without FXR and 10 microM with FXR. Deletion analysis revealed that the bile acid response element located between nucleotides -148 and -128 was the FXR response element, but RXRalpha/FXR did not bind to this sequence. These results suggest that bile acid-activated FXR exerts its inhibitory effect on CYP7A1 transcription by an indirect mechanism, in contrast to the stimulation and binding of FXR to intestinal bile acid-binding protein gene promoter. Results also reveal that bile acid receptors other than FXR are present in HepG2 cells.

Demosaicing: image reconstruction from color CCD samples.

A simplified color image formation model is used to construct an algorithm for image reconstruction from CCD sensors samples. The proposed method involves two successive steps. The first is motivated by Cok's template matching technique, while the second step uses steerable inverse diffusion in color. Classical linear signal processing techniques tend to oversmooth the image and result in noticeable color artifacts along edges and sharp features. The question is how should the different color channels support each other to form the best possible reconstruction. Our answer is to let the edges support the color information, and the color channels support the edges, and thereby achieve better perceptual results than those that are bounded by the sampling theoretical limit.

Cytotoxic effects of 2-butoxyethanol in vitro are related to butoxyacetaldehyde, an intermediate oxidation product.

Ethylene glycol ethers belong to a group of solvents with a wide spectrum of applications, particularly because of their compatibility to both hydrophilic and lipophilic systems. Especially ethylene glycol monobutyl ether (2-butoxyethanol, BE) is widely used as a key ingredient in many industrial and consumer cleaning products. Therefore, the risk of human exposure and toxicity by BE as well as its potential for environmental contamination have to be carefully evaluated. By using an established kidney epithelial cell line from the proximal tubule (opossum kidney cells), we investigated the effects of BE on viability, proliferative activity, volume and the organization of the intracellular cytoskeleton of the cells. The experiments were performed with freshly used BE and BE that had been stored at room temperature in the original packing for 3 months after use. After this period of storage the latter BE contained-besides butyraldehyde and n-butanol-0.5 vol% butoxyacetaldehyde (BAL) as measured by capillary gas chromatography and mass spectrometry. Freshly used BE did not cause a toxic effect in the in vitro assays at all concentrations tested (up to 1 mg/ml). In contrast, stored BE which contained BAL reduced cell viability and mitotic activity in a dose-dependent manner. The effective concentration of stored BE causing a 50% loss in cell viability (EC(50/24h)) was calculated to be 1 mg/ml. The toxic effect of stored BE also resulted in alterations of cell morphology and a depolymerization of actin-containing stress fibers. Moreover, administration of stored BE also caused a dose-dependent cell volume increase by the uptake of water, pointing to a necrotic process. In addition, synthesized BAL with a purity of 73.5% (gas chromatography) was also tested and caused an EC(50/24h) of 15 µg/ml, which is a 70-fold lower concentration when compared with stored BE. The present study provides evidence that BE possesses only a low cytotoxic potential in vitro, whereas the corresponding BAL, an intermediate in the oxidation process of BE to butoxyacetic acid, has marked toxic effects. The occurrence of the aldehyde might explain the predominant hematological effects of BE observed in vivo.

Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds.

In contrast to trivalent chromium (Cr(III)) compounds, hexavalent chromium ((Cr(VI)) compounds are oxidizing agents capable of directly inducing tissue damage and possessing carcinogenic, mutagenic and teratogenic potency. After oral or dermal absorption of Cr(VI), the kidney is the main target organ for chromium accumulation, which might result in acute tubular necrosis in humans. In contrast, an acute toxic effect of Cr(VI) on the liver has not yet been described. Therefore, we used two established epithelial cell lines from the kidney (Opossum kidney cells) and the liver (Hep G2 cells) to design an in vitro-assay which is able to examine acute toxic effects of chromium compounds. Cells of both cell lines were treated with various concentrations of Cr(III) and Cr(VI) ranging from 0.01 micromol/l to 1 mmol/l for 24 h. Thereafter, cell morphology, organization of the intracellular cytoskeleton, number of viable cells and mean cell volume were examined. The results show that Cr(VI), but not Cr(III), has an acute cytotoxic effect and causes a dose-dependent loss in cell viability. The effective dose that caused 50% of cell death was 5 micromol/l for kidney epithelial cells and 50 micromol/l for liver epithelial cells. This means that kidney epithelial cells are 10 times more sensitive towards Cr(VI) treatment than liver epithelial cells and this might explain the known nephrotoxicity in vivo. The loss in cell viability was accompanied by a rounding and detachment of the cells and a marked reduction of intracellular F-actin-containing stress fibers. Microtubules and intermediate-sized filaments were observed to be unaffected. Only in the case of kidney epithelial cells, a dose-dependent cell volume increase was observed after Cr(VI) treatment at concentrations up to 50 micromol/l. At higher concentrations, the cell volume decreased due to the high number of cells undergoing lysis and the appearance of cellular fragments. Various chloride channel blockers with different specificities, molecular structures and inhibitory potentials were tested for their ability to prevent Cr(VI)-induced cell damage. None of the channel blockers was able to inhibit cell damage, suggesting that the uptake of Cr(VI) through the general anion transport system of the cell membrane might be only one facet of cellular uptake and toxification. The data presented here not only confirm the different organ-specific effects of Cr(III) and Cr(VI), but also provide a basis for future experiments on the understanding of acute toxicity of Cr(VI) compounds. Moreover, the results demonstrate that the designed in vitro-assay might be a useful tool to prove whether non-toxic Cr(III) can be oxidized to Cr(VI) under specific industrial conditions (for example, in the leather or chrome industry).

Nephrotoxic effects of di-(2-ethylhexyl)-phthalate (DEHP) hydrolysis products on cultured kidney epithelial cells.

1. Di-(2-ethylhexyl)-phthalate (DEHP) possesses a great industrial value as a plasticizing agent and has become an ubiquitous environmental contaminant. In most species it is rapidly metabolized to mono-(2-ethylhexyl)-phthalate (MEHP) and 2-ethylhexanoic acid (2-EHA). Evaluation of toxicity of DEHP and its primary metabolites has been focussed on reproductive toxicity and hepatocarcinogenic properties. The aim of this study was to determine the nephrotoxic potential of both DEHP metabolites by use of cultured kidney epithelial cells (Opossum kidney cells; OK cells). 2. For this purpose, OK cells were exposed for 3 days to MEHP and 2-EHA at concentrations ranging from 0.1 -500 micromol/L and the toxicity as well as the effects on migratory activity and intracellular cytoskeleton were studied by cell biological, morphological and morphometric methods. 3. When compared with corresponding controls, treatment of OK cells with MEHP and 2-EHA, respectively, showed marked differences in cell viability between both DEHP metabolites. MEHP caused a dose-dependent decrease in cell viability (ED50 = 25 micromol/L) accompanied by a moderate swelling of the cells at concentrations up to 25 micromol/L. MEHP concentrations higher than 25 micromol/L caused a dose-dependent shrinkage of the cells and the occurrence of a high amount of cell debris as a result of cell lysis. 2-EHA did not cause a reduced viability or an altered cell volume. The migratory activity of OK cells was not significantly influenced by both metabolites. Moreover, MEHP toxicity resulted in a largely reduced and altered organization of F-actin (stress fibers), but not of myosin, microtubules and vimentin. 4. The study indicates that cultured epithelial cells can be used as a prescreening system to assess the nephrotoxicity of hazardous substances such as DEHP. As demonstrated in this study, only MEHP, but not 2-EHA, has a marked nephrotoxic effect in vitro.

Identification of novel stress-induced genes downstream of chop.

CHOP (GADD153) is a small nuclear protein that dimerizes avidly with members of the C/EBP family of transcription factors. Normally undetectable, it is expressed at high levels in cells exposed to conditions that perturb protein folding in the endoplasmic reticulum and induce an endoplasmic reticulum stress response. CHOP expression in stressed cells is linked to the development of programmed cell death and, in some instances, cellular regeneration. In this study, representational difference analysis was used to compare the complement of genes expressed in stressed wild-type mouse embryonic fibroblasts with those expressed in cells nullizygous for chop. CHOP expression, in concert with a second signal, was found to be absolutely required for the activation by stress of a set of previously undescribed genes referred to as DOCs (for downstream of CHOP). DOC4 is a mammalian ortholog of a Drosophila gene, Tenm/Odz, implicated in patterning of the early fly embryo, whereas DOC6 encodes a newly recognized homolog of the actin-binding proteins villin and gelsolin. These results reveal the existence of a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic reticulum unfolded protein response, which may mediate changes in cell phenotype in response to stress.

Computing geodesic paths on manifolds.

The Fast Marching Method is a numerical algorithm for solving the Eikonal equation on a rectangular orthogonal mesh in O(M log M) steps, where M is the total number of grid points. In this paper we extend the Fast Marching Method to triangulated domains with the same computational complexity. As an application, we provide an optimal time algorithm for computing the geodesic distances and thereby extracting shortest paths on triangulated manifolds.

Body fatness and increased injury rates in high school football linemen.

OBJECTIVE: To determine whether associations exist between body fatness and injury rates in high school football linemen. DESIGN: Prospective, injury surveillance study during a 2-week preseason and 10-week regular season. SETTING: 10 public high schools in Texas. PARTICIPANTS: Two hundred fifteen varsity and junior varsity high school football linemen. MAIN OUTCOME MEASURES: Injury rates (injuries per 1000 hours of playing time) for groups of players above a given body fat level and at or below a given body fat level. Rates were computed as the number of injuries per group divided by the group's aggregate playing time (practice + game time). The null hypothesis was that there is no difference in injury rates between players above a given level of body fat and those at or below that level of body fat. Body fat was determined from chest, abdomen, and thigh skinfold measurements using standard conversion equations. Body mass index (BMI) (kg/m2) was also calculated for each player. RESULTS: The overall injury rate was 5.66 injuries per 1000 hours of playing time. Percent body fat ranged from 9.3% to 40.2%. BMI ranged from 19.9 to 46.6 kg/m2. Sixty-seven players sustained 86 injuries, the most common of which were ankle sprains and medial collateral ligament sprains. No difference in overall injury rates between higher and lower fat groups was seen at any body fat level. Players in higher body fat groups, however, had significantly greater lower extremity injury rates than did players in lower fat groups between 18% and 27% body fat and again 32% to 33%, but not at intermediate levels or >33%. Players in higher BMI groups had significantly greater lower extremity injury rates than did players in lower BMI groups throughout the range from 24 to 36 kg/m2, except at 34 kg/m2. CONCLUSION: Both higher body fatness and BMI were associated with increased rates of lower extremity injury among high school football linemen. BMI appears to be associated more consistently with increased lower extremity injury rates than is body fat.

Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs.

The apical ectodermal ridge (AER), a rim of thickened ectodermal cells at the interface between the dorsal and ventral domains of the limb bud, is required for limb outgrowth and patterning. We have previously shown that the limbs of En1 mutant mice display dorsal-ventral and proximal-distal abnormalities, the latter being reflected in the appearance of a broadened AER and formation of ectopic ventral digits. A detailed genetic analysis of wild-type, En1 and Wnt7a mutant limb buds during AER development has delineated a role for En1 in normal AER formation. Our studies support previous suggestions that AER maturation involves the compression of an early broad ventral domain of limb ectoderm into a narrow rim at the tip and further show that En1 plays a critical role in the compaction phase. Loss of En1 leads to a delay in the distal shift and stratification of cells in the ventral half of the AER. At later stages, this often leads to development of a secondary ventral AER, which can promote formation of an ectopic digit. The second AER forms at the juxtaposition of the ventral border of the broadened mutant AER and the distal border of an ectopic Lmx1b expression domain. Analysis of En1/Wnt7a double mutants demonstrates that the dorsalizing gene Wnt7a is required for the formation of the ectopic AERs in En1 mutants and for ectopic expression of Lmx1b in the ventral mesenchyme. We suggest a model whereby, in En1 mutants, ectopic ventral Wnt7a and/or Lmx1b expression leads to the transformation of ventral cells in the broadened AER to a more dorsal phenotype. This leads to induction of a second zone of compaction ventrally, which in some cases goes on to form an autonomous secondary AER.

A general framework for low level vision.

We introduce a new geometrical framework based on which natural flows for image scale space and enhancement are presented. We consider intensity images as surfaces in the (x, I) space. The image is, thereby, a two-dimensional (2-D) surface in three-dimensional (3-D) space for gray-level images, and 2-D surfaces in five dimensions for color images. The new formulation unifies many classical schemes and algorithms via a simple scaling of the intensity contrast, and results in new and efficient schemes. Extensions to multidimensional signals become natural and lead to powerful denoising and scale space algorithms.