Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland

We have developed a mouse model of diet-induced obesity that shows numerous abnormalities relating to mammary gland function. Animals ate 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for -casein, whey acid protein, and -lactalbumin were all decreased immediately postpartum but recovered as lactation was established over 2–3 days. Expression of acetyl-CoA carboxylase (ACC)- mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the diet. Although obese animals consumed more calories in the nonpregnant and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis

At Physiological Temperatures the ATPase Rates of Shortening Soleus and Psoas Myofibrils Are Similar

AbstractWe obtained the temperature dependences of the adenosine triphosphatase (ATPase) activities (calcium-activated and relaxed) of myofibrils from a slow muscle, which we compared with those from a fast muscle. We chose rabbit soleus and psoas because their myosin heavy chains are almost pure: isoforms I and IIX, respectively. The Arrhenius plots of the ATPases are linear (4–35°C) with energies of activation for soleus myofibrils 155kJmol−1 (activated) and 78kJmol−1 (relaxed). With psoas myofibrils, the energies of activation were 71kJmol−1 (activated) and 60kJmol−1 (relaxed). When extrapolated to 42°C the ATPase rates of the two types of myofibril were identical: 50s−1 (activated) and 0.23s−1 (relaxed). Whereas with psoas myofibrils the Km for adenosine triphosphate (activated ATPase) is relatively insensitive to temperature, that for soleus myofibrils increased from 0.3μM at 4°C to 66.5μM at 35°C. Our results illustrate the importance of temperature when comparing the mechanochemical coupling in different types of muscle. We discuss the problem of how to reconcile the similarity of the myofibrillar ATPase rates at physiological temperatures with their different mechanical properties

Force Distribution in a Granular Medium

We report on systematic measurements of the distribution of normal forces exerted by granular material under uniaxial compression onto the interior surfaces of a confining vessel. Our experiments on three-dimensional, random packings of monodisperse glass beads show that this distribution is nearly uniform for forces below the mean force and decays exponentially for forces greater than the mean. The shape of the distribution and the value of the exponential decay constant are unaffected by changes in the system preparation history or in the boundary conditions. An empirical functional form for the distribution is proposed that provides an excellent fit over the whole force range measured and is also consistent with recent computer simulation data.Comment: 6 pages. For more information, see http://mrsec.uchicago.edu/granula

Stress transmission in granular matter

The transmission of forces through a disordered granular system is studied by means of a geometrical-topological approach that reduces the granular packing into a set of layers. This layered structure constitutes the skeleton through which the force chains set up. Given the granular packing, and the region where the force is applied, such a skeleton is uniquely defined. Within this framework, we write an equation for the transmission of the vertical forces that can be solved recursively layer by layer. We find that a special class of analytical solutions for this equation are L\'evi-stable distributions. We discuss the link between criticality and fragility and we show how the disordered packing naturally induces the formation of force-chains and arches. We point out that critical regimes, with power law distributions, are associated with the roughness of the topological layers. Whereas, fragility is associated with local changes in the force network induced by local granular rearrangements or by changes in the applied force. The results are compared with recent experimental observations in particulate matter and with computer simulations.Comment: 14 pages, Latex, 5 EPS figure

Properties of layer-by-layer vector stochastic models of force fluctuations in granular materials

We attempt to describe the stress distributions of granular packings using lattice-based layer-by-layer stochastic models that satisfy the constraints of force and torque balance and non-tensile forces at each site. The inherent asymmetry in the layer-by-layer approach appears to lead to an asymmetric force distribution, in disagreement with both experiments and general symmetry considerations. The vertical force component probability distribution is robust and in agreement with predictions of the scalar q model while the distribution of horizontal force components is qualitatively different and depends on the details of implementation.Comment: 18 pages, 12 figures (with subfigures), 1 table. Uses revtex, epsfig,subfigure, and cite. Submitted to PRE. Plots have been bitmapped. High-resolution version is available. Email [email protected] or download from http://rainbow.uchicago.edu/~mbnguyen/research/vm.htm

The prognostic significance of transforming growth factors in human breast cancer.

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome

Optimal network topologies for local search with congestion

The problem of searchability in decentralized complex networks is of great importance in computer science, economy and sociology. We present a formalism that is able to cope simultaneously with the problem of search and the congestion effects that arise when parallel searches are performed, and obtain expressions for the average search cost--written in terms of the search algorithm and the topological properties of the network--both in presence and abscence of congestion. This formalism is used to obtain optimal network structures for a system using a local search algorithm. It is found that only two classes of networks can be optimal: star-like configurations, when the number of parallel searches is small, and homogeneous-isotropic configurations, when the number of parallel searches is large.Comment: 4 pages. Final version accepted in PR