Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis

Objectives: To investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches. Methods: Epigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid). Results: OA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (ß=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (ß=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2a/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes. Conclusions: Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach

Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis

Objectives To investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches.Methods Epigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid).Results OA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (β=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (β=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2α/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes.Conclusions Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach.Computer Systems, Imagery and Medi

The impact of soil preparation on the soil erosion rates under laboratory conditions

Abstract. The use of laboratory methods in soil erosion studies causes soil disturbance, preparation and placement in experimental plots and has been recently considered more and more because of many advantages. However, different stages of soil removal, transfer, preparation and placement in laboratory plots cause significant changes in soil structure and subsequently, the results of runoff, sediment concentration and soil loss. Knowing the rate of changes in sediment concentration and soil loss variables with respect to the soil preparation for laboratory studies is therefore inevitable to generalize the laboratory results to field conditions. However, there has been less attention to evaluate the effects of soil preparation on sediment variables. The present study was therefore conducted to compare sediment concentration and soil loss in natural and prepared soil. To achieve the study purposes, 18 field 1 m × 1 m-plots were adopted in an 18% gradient slope with sandy-clay-loam soil in the Kojour watershed, Northern Iran. Three rainfall intensities of 40, 60 and 80 mm h−1 were simulated on both prepared and natural soil treatments with three replications. The sediment concentration and soil loss at five three-minute intervals after time-to-runoff were then measured. The results showed the significant (p ≤ 0.01) increasing effects of soil preparation on the average sediment concentration and soil loss. The increasing rates of runoff coefficient, sediment concentration and soil loss due to the study soil preparation method for laboratory soil erosion plots, were 179, 183 and 1050% (2.79, 2.83 and 11.50 times), respectively. </jats:p

The effects of watershed physical properties on bed load morphometric and sedimentologic characteristics along downstream: a case study from Ghalesar watershed in Mazandaran Province

Litnology and sedimentology factors affect on downstream changes in bed load shape and can be useful to detect watershed hydrological processes as they are very important to design hydraulic structures and reservoir management. This research was conducted in Qalesar River in Mazandaran Province with main river length of 24 Kilometers. After recognition of the study area, 11 sections were selected toward downstream for bed load sampling. Laboratory analysis were done using gravel meter and sieving method to measure and calculate some bed load shape characteristics. Also physical properties of each sub-watershed were extracted using Arc/GIS 9.2 software. Finally, in order to determine most effective physical characteristics on bed load shape, data were analyzed using SPSS 16. Results of statistical analysis indicate the best model between D50 and length of 1 order channel in bivariate regression equations and between D50 and distance from upstream in multi-variate regression equations

Service Architecture for 3rd Party Operator’s Participation

Abstract—Next generation networks with the idea of convergence of service and control layer in existing networks (fixed, mobile and data) and with the intention of providing services in an integrated network, has opened new horizon for telecom operators. On the other hand, economic problems have caused operators to look for new source of income including consider new services, subscription of more users and their promotion in using more network resources and easy participation of service providers or 3rd party operators in utilizing networks. With this requirement, an architecture based on next generation objectives for service layer is necessary. In this paper, a new architecture based on IMS model explains participation of 3rd party operators in creation and implementation of services on an integrated telecom network

The impact of standard preparation practice on the runoff and soil erosion rates under laboratory conditions

The use of laboratory methods in soil erosion studies, rainfall simulation experiments, Gerlach troughs, and other measurements such as ring infiltrometer has been recently considered more and more because of many advantages in controlling rainfall properties and high accuracy of sampling and measurements. However, different stages of soil removal, transfer, preparation and placement in laboratory plots cause significant changes in soil structure and, subsequently, the results of runoff, sediment concentration and soil loss. Knowing the rate of changes in sediment concentration and soil loss variables with respect to the soil preparation for laboratory studies is therefore inevitable to generalize the laboratory results to field conditions. However, there has been little attention given to evaluate the effects of soil preparation on sediment variables. The present study was therefore conducted to compare sediment concentration and soil loss in natural and prepared soil. To achieve the study purposes, 18 field 1 ×  1 m plots were adopted in an 18 % gradient slope with sandy–clay–loam soil in the Kojour watershed, northern Iran. A portable rainfall simulator was then used to simulate rainfall events using one or two nozzles of BEX: 3/8 S24W for various rainfall intensities with a constant height of 3 m above the soil surface. Three rainfall intensities of 40, 60 and 80 mm h⁻¹ were simulated on both prepared and natural soil treatments with three replications. The sediment concentration and soil loss at five 3 min intervals after time to runoff were then measured. The results showed the significant increasing effects of soil preparation (<i>p</i> ≤ 0.01) on the average sediment concentration and soil loss. The increasing rates of runoff coefficient, sediment concentration and soil loss due to the study soil preparation method for laboratory soil erosion plots were 179, 183 and 1050 % (2.79, 2.83 and 11.50 times), respectively