Fetal baboon sex-specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction.

OBJECTIVE: To investigate in vitro adipocyte differentiation in baboon fetuses in response to reduced maternal nutrition. DESIGN: Cross-sectional comparison of adipocyte differentiation in normally grown fetuses and fetuses of pregnant baboons fed 70% of the control global diet from 30 days of pregnancy to term. SUBJECTS: The subjects comprised control (CTR) fetuses (five female and five male) of mothers fed ad libitum and fetuses of mothers fed 70% of the global diet consumed by CTR (maternal nutrient reduction (MNR), five female and five male fetuses). The expression of genes/proteins involved in adipogenesis (PPARγ, FABP4 and adiponectin) and brown adipose tissue development (UCP1, TBX15 and COXIV) were determined in in vitro-differentiated stromal-vascular cultures from subcutaneous abdominal, subcutaneous femoral and omental adipose tissue depots. Adipocyte number per area (mm(2)) was determined histologically to assist in the evaluation of adipocyte size. RESULTS: Maternal suboptimal nutrition suppressed growth of male but not female fetuses and led to adipocyte hypertrophy accompanied by increased markers of white- and, particularly, brown-type adipogenesis in male but not female fetuses. CONCLUSION: Adipose tissue responses to fetal nonhuman primate undernutrition are sexually dimorphic. While female fetuses adapt adequately, the male ones enhance pathways involved in white and brown adipose tissue development but are unable to compensate for a delayed development of adipose tissue associated with intrauterine growth restriction. These differences need to be considered when assessing developmental programming of adiposity in response to suboptimal maternal nutrition.

Insulin receptor-independent upregulation of cellular glucose uptake.

BACKGROUND: Cellular glucose uptake can be enhanced by upregulating Ras signaling in either insulin-dependent or -independent manner. In presence of insulin and intact insulin signaling, Ras has a negligible role in glucose uptake. Conversely, when insulin signaling is impaired in obesity or diabetes, the insulin-independent Ras pathway may be valuable for enhancing glucose disposal. We previously reported that Ad36, a human adenovirus, enhances cellular glucose uptake by upregulating the Ras/Glut4 pathway. Here, we investigated if Ad36-upregulated Ras via the insulin-independent pathway, to enhance glucose uptake. Furthermore, uncontrolled upregulation of Ras is linked with oncogenic cell transformation, if the tumor-suppressor gene p53 is also downregulated. Hence, we determined if upregulation of Ras by Ad36 would induce oncogenic cell transformation. Finally, we determined the relevance of Ad36 to insulin resistance in humans. METHODS: Insulin receptor (IR) was knocked down with small interfering RNA in 3T3-L1 adipocytes, to determine if Ad36 increases the Ras/Glut4 pathway and glucose uptake without IR-signaling. Next, the effects of Ad36 on cell transformation and p53 abundance were determined. Finally, overweight or obese women were screened for seropositivity to Ad36, as an indicator of natural Ad36 infection. Associations of Ad36 infection with adiposity and C-reactive proteins (CRPs)-two key markers of insulin resistance, and with glucose disposal, were determined. RESULTS: Unaffected by IR knock-down, Ad36 significantly increased the Ras pathway, Glut4 translocation and glucose uptake in 3T3-L1 adipocytes. Despite Ras upregulation, Ad36 did not transform 3T3-L1 cells. This may be because Ad36 significantly increased p53 protein in 3T3-L1 cells or mice adipose tissue. Ad36 seropositivity was associated with greater adiposity and CRP levels, yet a significantly higher systemic glucose disposal rate. CONCLUSIONS: Overall, the study offers Ras/Glut4 pathway as an alternate to enhance glucose disposal when insulin signaling is impaired, and, importantly, provides Ad36 as a tool to understand the modulation of that pathway.

Template to improve glycemic control without reducing adiposity or dietary fat.

Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches.

A robust approach to image enhancement based on fuzzy logic.

In this paper, we propose a robust approach to image enhancement based on fuzzy logic that addresses the seemingly conflicting goals of image enhancement: (i) removing impulse noise, (ii) smoothing out nonimpulse noise, and (iii) enhancing (or preserving) edges and certain other salient structures. We derive three different filters for each of the above three tasks using the weighted (or fuzzy) least squares (LS) method, and define the criteria for selecting each of the three filters. The criteria are based on the local context, and they constitute the antecedent clauses of the fuzzy rules. The overall result of the fuzzy rule-based system is the combination of the results of the individual filters, where each result contributes to the degree that the corresponding antecedent clause is satisfied. This approach gives us a powerful and flexible image enhancement paradigm. Results of the proposed method on several types of images are compared with those of other standard techniques.

Implementation of parallel thinning algorithms using recurrent neural networks.

The use of recurrent neural networks for skeletonization and thinning of binary images is investigated. The networks are trained to learn a deletion rule and they iteratively delete object pixels until only the skeleton remains. Recurrent neural network architectures that implement a variety of thinning algorithms, such as the Rosenfeld-Kak algorithm and the Wang-Zhang (WZ) algorithm, are presented. A modified WZ algorithm which produces skeletons that are intuitively more pleasing is introduced.

The fuzzy c spherical shells algorithm: A new approach.

The fuzzy c spherical shells (FCSS) algorithm is specially designed to search for clusters that can be described by circular arcs or, generally, by shells of hyperspheres. A new approach to the FCSS algorithm is presented. This algorithm is computationally and implementationally simpler than other clustering algorithms that have been suggested for this purpose. An unsupervised algorithm which automatically finds the optimum number of clusters is not known. It uses a cluster validity measure to identify good clusters, merges all compatible clusters, and eliminates spurious clusters to achieve the final results. Experimental results on several data sets are presented.

Evidence aggregation networks for fuzzy logic inference.

Fuzzy logic has been applied in many engineering disciplines. The problem of fuzzy logic inference is investigated as a question of aggregation of evidence. A fixed network architecture employing general fuzzy unions and intersections is proposed as a mechanism to implement fuzzy logic inference. It is shown that these networks possess desirable theoretical properties. Networks based on parameterized families of operators (such as Yager's union and intersection) have extra predictable properties and admit a training algorithm which produces sharper inference results than were earlier obtained. Simulation studies corroborate the theoretical properties.

Hough transform detection of 3-D curves and target trajectories.

The problem of detecting curves and target trajectories in 3-D space is examined. Techniques based on the Hough transform and a 3-D extension of it are presented. The effectiveness of the techniques for the detection of circles and circular missile trajectories given two arbitrary 2-D views (or given sequences of one range image of point target trajectories) is illustrated. Simulation results indicate that performance is excellent, even in the presence of gaps in the input data.

Hough transform projections and slices for object discrimination and distortion estimation.

A new technique for determining the distortion parameters (location, orientation, and scale) of general 2-D objects is introduced. It uses the straight-line Hough transform as a feature space. The technique is very efficient and robust, since the dimensionality of the feature space is low and since it uses input images directly (with no preprocessing such as segmentation). Because the feature space allows separation of translation and rotation effects, a hierarchical algorithm to discriminate among objects and to detect object rotation and translation using projections and slices of the Hough space is possible.

Detection of target trajectories using the Hough transform.

Recently developed Hough transform techniques for curved object detection are applied to the detection of target trajectories. Multitarget missile trajectories are considered with noise present and missing data.

Optical associative processor for general linear transformations.

A new technique for the realization of general linear transformations using associative memories is described. An optical architecture for its implementation is also presented. A low-level feature space processor using this architecture is proposed. The processor is capable of recognizing and locating objects of various shapes and uses certain linear transformations in the feature space for distortion invariance.