HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes

HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown. Here we show that HOXA10 contributes to osteogenic lineage determination through activation of Runx2 and directly regulates osteoblastic phenotypic genes. In response to bone morphogenic protein BMP2, Hoxa10 is rapidly induced and functions to activate the Runx2 transcription factor essential for bone formation. A functional element with the Hox core motif was characterized for the bone-related Runx2 P1 promoter. HOXA10 also activates other osteogenic genes, including the alkaline phosphatase, osteocalcin, and bone sialoprotein genes, and temporally associates with these target gene promoters during stages of osteoblast differentiation prior to the recruitment of RUNX2. Exogenous expression and small interfering RNA knockdown studies establish that HOXA10 mediates chromatin hyperacetylation and trimethyl histone K4 (H3K4) methylation of these genes, correlating to active transcription. HOXA10 therefore contributes to early expression of osteogenic genes through chromatin remodeling. Importantly, HOXA10 can induce osteoblast genes in Runx2 null cells, providing evidence for a direct role in mediating osteoblast differentiation independent of RUNX2. We propose that HOXA10 activates RUNX2 in mesenchymal cells, contributing to the onset of osteogenesis, and that HOXA10 subsequently supports bone formation by direct regulation of osteoblast phenotypic genes. <br/

Nuclear structure-gene expression interrelationships: implications for aberrant gene expression in cancer

There is long-standing recognition that transformed and tumor cells exhibit striking alterations in nuclear morphology as well as in the representation and intranuclear distribution of nucleic acids and regulatory factors. Parameters of nuclear structure support cell growth and phenotypic properties of cells by facilitating the organization of genes, replication and transcription sites, chromatin remodeling complexes, transcripts, and regulatory factors in structurally and functionally definable subnuclear domains within the three-dimensional context of nuclear architecture. The emerging evidence for functional interrelationships of nuclear structure and gene expression is consistent with linkage of tumor-related modifications in nuclear organization to compromised gene regulation during the onset and progression of cancer

Визначення правового статусу садівницьких, городницьких та дачних товариств

Розкриваються особливості правового статусу садівницьких, городницьких та дач­них товариств, досліджується їх організаційно-правова форма та ті специфічні пра­вові ознаки, що знаходяться в її основі. У зв’язку з відсутністю правової бази діяль­ності цих товариств, робиться спроба сформувати основні теоретико-правові кон­цептуальні підходи до розуміння їх природи та змоделювати законодавчу схему регулювання їх діяльності.Раскрываются особенности правового статуса садоводческих, огороднических и дачных товариществ, исследуются их организационно-правовая форма и правовые особенности, составляющие ее основание. В связи с отсутствием правовых обоснований деятельности этих товариществ автор стремится сформировать основные теоре­тико-правовые концептуальные подходы к раскрытию их сущности и смоделировать законодательную схему регулирования деятельности рассматриваемых товариществ.In article features of legal status of garden, vegetable-garden and country companies reveal, their organizational legal form and those specific features that are in its basis are investigated. In connection with absence of legal base of activity of these communities is attempted to generate the basic theoretical-legal conceptual approaches to understanding of their nature and model legislative sphere of regulation of their activity becomes

Dose-dependent effects of exogenous gonadotrophins on the endometrium of the rat

We compared the serwn levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and hwnan chorionic gonadotrophin (HCG). Evidence of ovarian hyperstimulation was observed in the high- but not the low-dose group; both treatment regimens caused significant changes in the endometrial surface, epithelial height, the microvillous border, the glycocalyx, the subepithelial stromal cells and the mitotic activity of the surface epithelial and stromal connective tissue cells. The effects of the highdose treatment were Inore severe than those of the low-dose treatment. The serum oestradiol and progesterone levels of the treated groups were not significantly different from those of the control group. The changes in the endometrium after both treatment regimens may interfere with normal trophoblastic-endometrial interactions and could influence the maintenance of pregnancy. This investigation demonstrated that even low doses of gonadotrophins, which do not cause obvious ovarian stimulation, affect uterine morphology. The findings haveimportant implications for in vitro fertilisation and embryo transfer programmes

Stabilized immersed isogeometric analysis for the Navier-Stokes-Cahn-Hilliard equations, with applications to binary-fluid flow through porous media

Binary-fluid flows can be modeled using the Navier-Stokes-Cahn-Hilliard equations, which represent the boundary between the fluid constituents by a diffuse interface. The diffuse-interface model allows for complex geometries and topological changes of the binary-fluid interface. In this work, we propose an immersed isogeometric analysis framework to solve the Navier-Stokes-Cahn-Hilliard equations on domains with geometrically complex external binary-fluid boundaries. The use of optimal-regularity B-splines results in a computationally efficient higher-order method. The key features of the proposed framework are a generalized Navier-slip boundary condition for the tangential velocity components, Nitsche's method for the convective impermeability boundary condition, and skeleton- and ghost-penalties to guarantee stability. A binary-fluid Taylor-Couette flow is considered for benchmarking. Porous medium simulations demonstrate the ability of the immersed isogeometric analysis framework to model complex binary-fluid flow phenomena such as break-up and coalescence in complex geometries

The KINDRA project – towards Open Science in Hydrogeology for higher impact

Groundwater knowledge and research in the European Union is often scattered and non-standardised. Therefore, KINDRA is conducting an EU-wide assessment of existing groundwater-related practical and scientific knowledge based on a new Hydrogeological Research Classification System (HRC-SYS). The classification is supported by a web service, the European Inventory of Groundwater Research (EIGR), which acts not only as a knowledge repository but also as a tool to help identify relevant research topics, existing research trends and critical research challenges. These results will be useful for producing synergies, implementing policies and optimising water management in Europe. This article presents the work of the project during the first two years in relation to a common classification system and an activity for data collection and training delivered by the EFG’s National Associations in 20 European countries

GSAreport: easy to use global sensitivity reporting

NWO19455Algorithms and the Foundations of Software technolog

Concerted control of multiple histone promoter factors during cell density inhibition of proliferation in osteosarcoma cells: reciprocal regulation of cell cycle-controlled and bone-related genes

Cell density-induced growth inhibition of osteosarcoma cells (ROS 17/2.8) results in the shutdown of proliferation-specific histone H4 and H2B genes and the concomitant up-regulation of several osteoblast-related genes. In several respects, this reciprocal regulatory relationship is analogous to the proliferation/differentiation transition stage during development of the bone cell phenotype in normal diploid osteoblasts. Here, we comprehensively analyzed the promoter binding activities interfacing with key regulatory elements in the cell cycle-dependent histone and bone-specific osteocalcin genes. Similarly, we examined factors interacting with a series of general transcription regulatory elements that are present in a broad spectrum of promoters. The results show that histone promoter binding activities HiNF-D, HiNF-P/H4TF-2, H4UA-1, and OCT-1, as well as AP-1 activity, are proliferation dependent. These factors decline coordinately during the cessation of proliferation in both ROS 17/2.8 bone tumor cells and normal diploid osteoblasts. Collective down-regulation of these trans-activating factors occurs in both cell types within the physiological context of constitutive regulation of ubiquitous transcription factors (Sp1, ATF, and CCAAT binding proteins). In addition, during growth inhibition of ROS 17/2.8 cells we observe a complex series of modifications in protein/DNA interactions of the osteocalcin gene. These modifications include both increased and decreased representation of promoter factor complexes occurring at steroid hormone response elements as well as tissue-specific basal promoter sequences. These results demonstrate cell growth regulation of the promoter factors binding to the proliferation-specific histone and tissue-specific osteocalcin genes during the cessation of proliferation

GSAreport: easy to use global sensitivity reporting

NWO19455Algorithms and the Foundations of Software technolog