Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

A formal description of open distributed processing (ODP) trading based on guidelines for the definition of managed objects (GDMO)

New requirements of growing computer networks and information systems have an influence on extended client/server models with increased functionality. This forms the basis for service management in distributed systems which is realized by a service trading concept. This paper studies the requirements derived from the Open Distributed Processing (ODP) Reference Model in order to consider an open service market. Furthermore, it examines management possibilities for describing the service trading scenario. Because of similar architectures and properties ODP services, service offers, types, exporters and traders are mapped onto management components and modeled as managed objects. Therefore, the Guidelines for the Definition of Managed Objects (GDMO) are used. The final concept allows a precise and unambiguous study of the service trading scenario and provides means for exporting and importing of service offers in a distributed environment.     

Specific interactions in blends containing Chitosan and functionalized polymers. Molecular dynamics simulations

Chitosan (CS)/poly(vinyl alcohol) (PVA) and Chitosan/poly(2-hydroxyethyl methacrylate) (P2HEM) blends have been studied through molecular dynamic simulations. In a previous work it was found miscibility between these polymers and it was attributed to hydrogen bonding formation. However, the experimental information obtained was not enough to know which of the interacting groups of Chitosan, i.e. -CH₂OH or -NH₂, are responsible of the interaction. Therefore, we have performed molecular dynamics simulation runs of 1 ns in order to calculate radial distribution functions (RDF) for the groups tentatively involved in the interaction. The results are correlated with our previous experimental data. This way, we have obtained a more precise conclusive information about the interactions involved as function of the blends composition. For low compositions of PVA and P2HEM the interaction is predominantly with the hydroxymethyl groups of CS while as the composition of PVA and P2HEM increases, the interaction with the amine groups increases.     

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

High Throughput Primer Walking of cDNA Clones

Primer walking of cloned DNA is a standard research tool. It has been used in the past to determine the sequence of individual clones of interest. With the expansion of DNA sequencing capacity the need to be able to walk larger numbers of clones has become necessary. Our laboratory is a mid-sized genomics facility. In conjunction with the Advanced Biomedical Computing Center (ABCC) we have developed methods for automating the primer selection, DNA sequencing, contig assembly and sequence analysis for clones arrayed in microtiter format. This approach has allowed us to walk 475 clones (five microtiter plates) selected from a cDNA library.     

On the performance of error control coding with diversity formobile channels

Upper bounds on the bit error probability are applied to evaluate the error performance of coded systems over non-interleaved and partially interleaved Rician fading mobile channels. The correlation between successive received symbols is exploited to bound the error performance. The bound allows useful evaluation of coding gains on realistic communication systems without going into lengthy computer simulations. By further defining the maximum energy degradation factors, compact upper bounds are expressed in a similar way as on the fully interleaved or memoryless channels. The maximum energy degradation factors are computed for a wide variety of mobile channel conditions. These factors give an interesting evaluation of the fading conditions and may be used to design coded communication systems on mobile channels. Furthermore, independent space or frequency diversity may be taken into account in these bounds and it is shown that the energy degradation due to correlation is independent of this added independent diversity