Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology

Gestational diabetes (GDM) is among the most challenging diseases in westernized countries, affecting mother and child, immediately and in later life. Obesity is a major risk factor for GDM. However, the impact visceral obesity and related epigenetics play for GDM etiopathogenesis have hardly been considered so far. Our recent findings within the prospective 'EaCH' cohort study of women with GDM or normal glucose tolerance (NGT), showed the role, critical factors of insulin resistance (i.e., adiponectin, insulin receptor) may have for GDM pathophysiology with epigenetically modified expression in subcutaneous (SAT) and visceral (VAT) adipose tissues. Here we investigated the expression and promoter methylation of key inflammatory candidates, tumor necrosis factor-alpha (TNF-α) and suppressor of cytokine signaling 3 (SOCS3) in maternal adipose tissues collected during caesarian section (GDM, n = 19; NGT, n = 22). The mRNA expression of TNF-α and SOCS3 was significantly increased in VAT, but not in SAT, of GDM patients vs. NGT, accompanied by specific alterations of respective promoter methylation patterns. In conclusion, we propose a critical role of VAT and visceral obesity for the pathogenesis of GDM, with epigenetic alterations of the expression of inflammatory factors as a potential factor

Considerations about the effectiveness and cost effectiveness of therapies in the treatment of hyperphosphataemia

Because of an elevated serum phosphate level, patients who suffer from chronic kidney failure frequently tend to have cardiovascular calcification and are therefore exposed to a higher probability of a fatal event. Phosphate binders are able to reduce these negative effects. Currently, there are primarily two groups of phosphate binders (calcium-containing and calcium-free phosphate binders) which are considered to be almost equally effective in terms of binding of free phosphate. There are, however, a few disadvantages of the two groups. While the calcium-containing binders are associated with an increased risk of hypercalcaemia, which is dose dependent, calcium-free binders have been criticized as being too expensive. As the expenditure for patients suffering from chronic kidney failure increases from year to year, as a result of increasing prevalence, there is a growing need for an alternative to existing phosphate binders. The study presented here therefore summarizes available information for the novel combination preparation OsvaRen® (calcium acetate/magnesium carbonate) as an alternative therapy to the calcium-free phosphate binder Renagel® (sevelamer-hydrochloride) and to calcium-containing preparations. The results of this systematic review showed that OsvaRen® is at least equally effective in the regulation of serum phosphate level as Renagel®. In particular, OsvaRen® shows no clinically relevant difference in terms of the control of the serum calcium levels compared to Renagel® and thereby does not increase the risk of a hypercalcaemia, in contrast to pure calcium-based phosphate binders. On the other hand, Renagel® therapy is much more frequently associated with gastrointestinal side-effects, a tendency to result in higher tablet burden for patients and high medication costs. The CALMAG study showed that OsvaRen® was at least as effective and safe in terms of controlling serum phosphate and serum calcium levels as Renagel® while, at the same time, resulting in about 80% lower costs. In addition, OsvaRen® offers a lower risk of hypercalcaemia and associated subsequent costs and is thereby also superior to pure calcium-containing phosphate binders. Because of the effectiveness and tolerability of calcium acetate/magnesium carbonate, OsvaRen® offers a clinically suitable and, at the same time, cost-effective therapeutic option in the therapy of hyperphosphataemia.Fresenius Medical Care Deutschland Gmb

Aging in vitro and D-glucose uptake kinetics of diploid human fibroblasts

By use of a rapid technique, initial rates of D-glucose transport were obtained during the lifespan in vitro of a commercially available strain of human embryo lung fibroblasts (Flow 2000). The apparent Km of the D-glucose carrier did not change during senescence in vitro: = 1.8 mM (range 1.3-2.3) in phase II, = 1.8 mM (range 1.5-2.2) in phase III. Transport rates remained constant in stationary phase II cultures, which had completed between 30% and 80% of their replicative lifespan. A wide variation, however, was observed in terminally differentiated cells (phase III), which showed a two- to threefold increase in average cell size and protein content. In some senescent cultures, glucose transport calculated on a per cell basis was also two-to threefold increased, while it was strongly decreased (-75%) in others. When calculated per unit of cell water, protein, and surface area, respectively, transport rates in phase III cultures ranged from values established for stationary phase II cultures down to very low values. Detaching cells flushed off from senescent cultures did not show measurable rates of glucose transport into the inulin impermeable cell space. Present evidence argues against the idea that an impairment of D-glucose transport might precede loss of replicative potential in aging human fibroblasts. Instead our data indicate that the transport capacity of cell membrane finally decreases during postreplicative senescence in terminally differentiated cells

Fuzzy logic-based approximate event notification in sparse MANETs

Mobile Ad-Hoc Networks (MANETs) are an important communication infrastructure to support emergency and rescue operations. To address the frequent disconnections and network partitions that might occur, we have developed a distributed event notification service (DENS) for sparse MANETs. In most event notification solutions, subscriptions are formed with crisp values or crisp value ranges. However, in emergency and rescue operations subscribers may not always have time to give crisp values or crisp value ranges. Moreover, subscriber's interests in queries have gradual nature and subjective measure that calls for computing by words. Therefore, we design and implement a simple fuzzy concept based subscription language allowing more expressive subscriptions and more sophisticated event-filtering. It is built on two new ideas: using features as multi-attribute indexes of the subscription and predicate patterns for processing subscriptions with arbitrary Boolean operators. However, requiring more computational efforts, fuzzy logic introduces performance penalties in the whole network. The proposed services have been evaluated for run-time, space and scalability efficiency. The proposed design framework is extensible to the user- and application-semantics and configurable to the dynamics in data that publish/subscribe paradigm imposes at runtime

DNA methylation and expression of proopiomelanocortin (POMC) gene in the hypothalamus of three-week-old chickens show sex-specific differences

Increased availability and improved sequence annotation of the chicken (Gallus gallus f. domestica) genome have sparked interest in the bird as a model system to investigate translational embryonic development and health/disease outcomes. However, the epigenetics of this bird genome remain unclear. The aim of this study was to determine the levels of gene expression and DNA methylation at the proopiomelanocortin (POMC) gene in the hypothalamus of 3-week-old chickens. POMC is a key player in the control of the stress response, food intake, and metabolism. DNA methylation of the promoter, CpG island, and gene body regions of POMC were measured. Our data illustrate the pattern, variability, and functionality of DNA methylation for POMC expression in the chicken. Our findings show correlation of methylation pattern and gene expression along with sex-specific differences in POMC. Overall, these novel data highlight the promising potential of the chicken as a model and also the need for breeders and researchers to consider sex ratios in their studies

ILORIN: Identifier-locator resolution for infrastructure-less networks

This word is at: 2012 Third International Conference on the Network of the Future (NOF) took place 21-23 November in Tunis, Tunisia. web event http://www.ati.es/spip.php?article2118In order to overcome the limitations of the current Internet addressing, it is generally accepted that the Future Internet needs a separation between identifiers and network locators. Such identifier-locator split is also needed in infrastructureless networks, such as Mobile ad hoc Networks (MANETs) and Delay Tolerant Networks, since they are an integral part of the Future Internet. Despite the amount of work in infrastructurebased networks, only a few proposals have considered how to apply this identifier-locator split in infrastructure-less networks. The contribution of this paper is an identifier-locator resolution system that can work in sparse MANETs, which are prone to network partitions. Our approach is an identifier-locator association discovery system, which uses periodic beacons to exchange the resolution information, avoiding the establishment of shared state between nodes. Our system exploits the broadcast nature of the wireless medium, opportunistic encounters, and information replication to disseminate identifier-locator associations across the network. The results of our extensive experiments demonstrate that our solution outperforms the related work, achieving a higher identifier-locator association discovery rate. Index Terms—Identifier-Locator split, Resolution system, Mobile Ad Hoc Network, Delay Tolerant Network.This work has been funded by the VERDIKT Programme of the Norwegian Research Council throughthe DT-Stream project (project number 183312/S10) and the Regional Government of Madrid through the MEDIANET project (MEDIANET S2009/TIC-1468)Publicad

Using routing information to optimize synchronization of replicated event notification mediators in sparse MANETs

Mobile Ad-Hoc Networks maintain information about reachable nodes in the routing table. In many application scenarios, human groups play an important role. This is visible at the network level as independent network partitions which are for some time stable before their members change through merging or partitioning. We use the information from stable routing tables to optimize the synchronization of Mediators in our Distributed Event Notification System. In a stable partition each node has the same information, thus a single Mediator can efficiently coordinate the synchronization, while all other Mediators just receive updates. We show in our experiments that just a few seconds are needed until routing tables stabilize and all nodes have a common view of the partition. We present a heuristic which each individual node uses to determine the proper time to synchronize. Furthermore, we show how exceptions, like disappearing coordinating Mediators and unexpected messages, can be efficiently handled

Visceral adipose tissue alteration of PI3KR1 expression is associated with gestational diabetes but not promoter DNA methylation

Obesity and diabetes are at an epidemic rate, as well as growing incidences of gestational diabetes mellitus (GDM) which causes pregnancy risks, and harm in both maternal and child health. It remains unclear which molecular mechanisms are driving the functional differences between visceral and subcutaneous fat and how these types directly affect an individual's health outcome. Paired abdominal subcutaneous and omental visceral adipose tissue were collected from women with GDM (n = 20) and with normal glucose tolerance (NGT, n = 22) during planned caesarian section. Both groups had similar maternal age (average 32.5 years) and BMI at delivery (average 33.3 kg/m2). Adipose tissue mRNA expression analyses of insulin signalling genes: PI3KCA, PI3KR1, IRS1 and IRS2 showed significantly decreased PI3KR1 expression (-23%) in visceral fat in GDM with no association to promoter DNA methylation. Reduced visceral fat PI3KR1 expression appears to be a pathogenic factor in GDM but not through altered promoter methylation