Dynamic of lipid droplets and gene expression in response to beta-aminoisobutyric acid treatment on 3T3-L1 cells

Research on adipobiology has recognized the browning process of white adipocytes as a potential therapeutic strategy for the treatment of obesity and related morbidities. Physical exercise stimulates the secretion of myokines, such as \uf062-aminoisobutyric acid (BAIBA), which in turn promotes adaptive thermogenesis. White adipocyte conversion to brown cells involves dynamic changes in lipid droplet (LD) dimension and in the transcription of brown-specific marker genes. This study analyzes the effect of different doses of BAIBA and at different days of development on 3T3-L1 cells by evaluating morphological changes in LDs and the expression of browning gene markers. Results suggested that the highest concentration of BAIBA after 4 days of differentiation produced the most significant effects. The number of LDs per cell increased in comparison to control cells, whereas the surface area significantly decreased. Brown adipocyte markers were up-regulated, but the effect of treatment was lost at 10 days of differentiation. The thermogenic program induced by BAIBA may reflect a rapid adaptation of adipose tissue to physical exercise. This connection stresses the beneficial impact of physical exercise on metabolic health

On kk-Core Percolation in Four Dimensions

The $k$-core percolation on the Bethe lattice has been proposed as a simple model of the jamming transition because of its hybrid first-order/second-order nature. We investigate numerically $k$-core percolation on the four-dimensional regular lattice. For $k=4$ the presence of a discontinuous transition is clearly established but its nature is strictly first order. In particular, the $k$-core density displays no singular behavior before the jump and its correlation length remains finite. For $k=3$ the transition is continuous

MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker

Recent advances in ruminants\u2019 milk\u2010derived exosomes (EXO) have indicated a role of microRNAs (miRNAs) in cell\u2010to\u2010cell communication in dairy ruminants. The miRNAs EXO retain peculiar mechanisms of uptake from recipient cells, which enables the selective delivery of cargos, with a specific regulation of target genes. Although many studies have been published on the miRNAs contained in milk, less information is available on the role of miRNAs EXO, which are considered stable over time and resistant to digestion and milk processing. Several miRNAs EXO have been implicated in the cellular signaling pathway, as in the regulation of immune response. Moreover, they exert epigenetic control, as extenuating the expression of DNA methyltransferase 1. However, the study of miRNAs EXO is still challenging due to the difficulty of isolating EXO. In fact, there are not agreed protocols, and different methods, often time\u2010consuming, are used, making it difficult to routinely process a large number of samples. The regulation of cell functions in mammary glands by miRNAs EXO, and their applications as genomic markers in livestock, is presented

Relationship between lipid droplets size and integrated optical density

Lipid accumulation is largely investigated due to its role in many human diseases. The attention is mainly focused on the lipid droplets (LDs), spherical cytoplasmic organelles which are devoted to the storage of the lipids. The amount of lipid content is often evaluated by measuring LDs size and/or the integrated optical density (IOD) in cultured cells. Both evaluations are directly associated to the lipid content and therefore they are correlated to each other, but a lack of theoretical relationship between size and IOD was observed in literature. Here we investigated the size-IOD relationship of LDs observed in microscopical images of cultured cells. The experimental data were obtained from immature and differentiated 3T3-L1 murine cells, which have been extensively used in studies on adipogenesis. A simple model based on the spherical shape of the LDs and the Lambert-Beer law, which describes the light absorption by an optical thick material, leads to a mathematical relationship. Despite only light rays\u2019 absorption was considered in the model, neglecting their scattering, a very good agreement between the theoretical curve and the experimental data was found. Moreover, a computational simulation corroborates the model indicating the validity of the mathematically theoretical relationship between size and IOD. The theoretical model could be used to calculate the absorption coefficient in the LDs population and it could be applied to seek for morphologically and functionally LDs subpopulations. The identification of LDs dynamic by measuring size and IOD could be related to different pathophysiological conditions and useful for understand cellular lipid-associated diseases

Characterizing and Improving Generalized Belief Propagation Algorithms on the 2D Edwards-Anderson Model

We study the performance of different message passing algorithms in the two dimensional Edwards Anderson model. We show that the standard Belief Propagation (BP) algorithm converges only at high temperature to a paramagnetic solution. Then, we test a Generalized Belief Propagation (GBP) algorithm, derived from a Cluster Variational Method (CVM) at the plaquette level. We compare its performance with BP and with other algorithms derived under the same approximation: Double Loop (DL) and a two-ways message passing algorithm (HAK). The plaquette-CVM approximation improves BP in at least three ways: the quality of the paramagnetic solution at high temperatures, a better estimate (lower) for the critical temperature, and the fact that the GBP message passing algorithm converges also to non paramagnetic solutions. The lack of convergence of the standard GBP message passing algorithm at low temperatures seems to be related to the implementation details and not to the appearance of long range order. In fact, we prove that a gauge invariance of the constrained CVM free energy can be exploited to derive a new message passing algorithm which converges at even lower temperatures. In all its region of convergence this new algorithm is faster than HAK and DL by some orders of magnitude.Comment: 19 pages, 13 figure

The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate

Simple Summary A number of skeletal disorders, all characterized by a metabolic or neoplastic loss of bone tissue, are cured with drugs called Bisphosphonates (BPs), which exert their therapeutic effect by suppressing cells named osteoclasts, normally mediating bone resorption. Unfortunately, these drugs can also provoke a dangerous side effect known as osteonecrosis of the jaw (ONJ), a bone infection localized in the oral cavity and characterized by gingival ulceration, sometimes accompanied by suppuration and pain. This condition, occasionally arising spontaneously, is more often started by a tooth extraction. The reduced number of osteoclasts, determined by BPs, is thought to favor the bacterial invasion of healthy bone and the incapacity to eliminate infected bone, that are in turn responsible for the appearance of ONJ. Here we show that Magnesium, used for decades as dietary supplement, can invert the effect of BPs, transforming them, through a sort of paradox effect, into powerful activators of osteoclast production. These results suggest that Magnesium might be used in a topical approach aimed to cure or prevent ONJ. Notably, the capacity of Magnesium to activate osteoclast production was even observed in absence of BPs, suggesting its application also in ONJ forms caused by agents distinct to BPs.Abstract Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ

Replica Cluster Variational Method: the Replica Symmetric solution for the 2D random bond Ising model

We present and solve the Replica Symmetric equations in the context of the Replica Cluster Variational Method for the 2D random bond Ising model (including the 2D Edwards-Anderson spin glass model). First we solve a linearized version of these equations to obtain the phase diagrams of the model on the square and triangular lattices. In both cases the spin-glass transition temperatures and the tricritical point estimations improve largely over the Bethe predictions. Moreover, we show that this phase diagram is consistent with the behavior of inference algorithms on single instances of the problem. Finally, we present a method to consistently find approximate solutions to the equations in the glassy phase. The method is applied to the triangular lattice down to T=0, also in the presence of an external field.Comment: 22 pages, 11 figure

Assessing Cancer Risk from Heavy Metals in Recycling Waste Electrical and Electronic Equipment: Preliminary Results from the WEENMODELS European Life Programme

Introduction The growing amount of waste derived from electrical and electronic equipment (WEEE) poses significant challenges to waste management, due to the presence of toxic chemicals with environmental and health implications for the general population and for occupationally-exposed workers. Methods Based on an toxicological and epidemiologic evaluation, we carried out a health risk assessment to evaluate the cancer risk deriving from environmental and occupational exposure to heavy metals released during different WEEE recycling procedures (electronic scrap in blister copper, treatment of metals recovery in copper smelter, treatment of shredding, pyrometallurgical treatment of Li-ion battery). We considered the typical WEEE production in a municipality of 150.0000 inhabitants, carrying out a Life Cycle Assessment. Outdoor (1 square km around a treatment plant) and indoor (for a factory volume of 3200 m3) emissions generated during the WEEE recycling procedures were computed. In particular, we estimated the amount of Cd, Ni and As inhaled by the potentially exposed population. We computed the cancer risk due to inhalation of these heavy metals in residents and workers using the methodology proposed by the California Office of Environmental Health and Hazard Assessment Results For the metals considered, our results showed negligible cancer risk (from 2,21x10-11 to 4,31x10-08) for the general population around the plant. On the converse, occupational exposures linked to specific procedures were associated with a cancer risk of 1,42x10-3 for workers in the shredding procedures mainly due to Ni exposure, and of 4,68x10-4 for workers with electronic scrap and exposed to As. Conclusions Based on our preliminary results from an integrated toxicological and epidemiologic approach, WEEE life cycle may be linked to health risks for workers in the recycling procedures, while it does not seem to adversely affect health of the general population around the treatment plants

CANCER RISK FROM HEAVY METAL EXPOSURE IN RECYCLING WASTE OF ELECTRICAL AND ELECTRONIC EQUIPMENT: PRELIMINARY RESULTS FROM THE WEEENMODELS EUROPEAN LIFE PROGRAM

Background and objectives: When electrical and electronic equipment reaches its end of life, it becomes ‘Waste Electrical and Electronic Equipment’ (WEEE). The growing amount of this type of waste has posed significant challenges to waste management, since WEEE contains a whole range of toxic chemicals having relevant environmental and health implications. The WEEE life cycle may expose the general population and workers to various toxic chemicals, such as heavy metals. We conducted a health risk assessment to evaluate the cancer risk derived from environmental and occupational exposure to trace elements from different recycling procedures (electronic scrap in blister copper, treatment of metals recovery in copper smelter, treatment of shredding, pyrometallurgical treatment of Li-ion battery). We considered the typical production of WEEE in a municipality of 150.0000 inhabitants, where a Life Cycle assessment (LCA) was carried out. Methods: Outdoor (1km2 around a WEEE treatment plant) and indoor (factory volume of 3200m3) emissions generated from the above-mentioned procedures were computed, to perform a health risk assessment for occupationally-exposed workers and for the general population around the plant. Dose of the heavy metals cadmium, nickel, arsenic inhaled by the potentially exposed population was estimated using the values obtained through a toxicological model. Cancer risk due to inhalation was calculated using the method proposed by the California Office of Environmental Health and Hazard Assessment. Results and Conclusions: For the heavy metals considered, generated from WEEE treatment, these preliminary results show negligible cancer risk for the general population. On the converse, some risks may be present for occupational exposures linked to specific procedures (from cancer risk of 1,42x10-3 for men working in shredding procedure and exposed to nickel to cancer risk of 4,68x10- 4 for women working with electronic scrap and exposed to arsenic)