Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-g production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses

The possible functions of duplicated ets (GGAA) motifs located near transcription start sites of various human genes

Transcription is one of the most fundamental nuclear functions and is an enzyme complex-mediated reaction that converts DNA sequences into mRNA. Analyzing DNA sequences of 5′-flanking regions of several human genes that respond to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in HL-60 cells, we have identified that the ets (GGAA) motifs are duplicated, overlapped, or clustered within a 500-bp distance from the most 5′-upstream region of the cDNA. Multiple protein factors including Ets family proteins are known to recognize and bind to the GGAA containing sequences. In addition, it has been reported that the ets motifs play important roles in regulation of various promoters. Here, we propose a molecular mechanism, defined by the presence of duplication and multiplication of the GGAA motifs, that is responsible for the initiation of transcription of several genes and for the recruitment of binding proteins to the transcription start site (TSS) of TATA-less promoters

Methodology of calculation of construction and hydrodynamic parameters of a foam layer apparatus for mass-transfer processes

Промислова реалізація методу стабілізації газорідинного шару дозволяє значно розширити галузь застосування пінних апаратів і відкриває нові можливості інтенсифікації технологічних процесів з одночасним створенням маловідходних технологій. У статті встановлені основні параметри, що впливають на гідродинаміку пінних апаратів, розглянуті основні конструкції та режими роботи пінних апаратів. Виявлено зв'язок гідродинамічних параметрів. Розглянуто гідродинамічні закономірності пінного шару. Вказані фактори, що впливають на процес масообміну, як в газовій, так і в рідкій фазах. Проведений аналіз ряду досліджень показав, що перспективним напрямком інтенсифікації процесу масообміну є розробка апаратів з трифазним псевдозрідженим шаром зрошуваної насадки складних форм із сітчастих матеріалів. Отже, необхідне проведення спеціальних досліджень гідродинамічних режимів роботи апарату з сітчастою насадкою і визначенням параметрів, що впливають на швидкість переходу насадки з одного режиму в інший.Industrial implementation of the stabilization method of the gas-liquid layer can significantly expand the field of use of foaming apparatus and opens up new opportunities for intensifying technological processes with the simultaneous creation of low-waste technologies. The article establishes the basic parameters influencing the hydrodynamics of foam apparatus, considers the basic constructions and operating modes of foam apparatus. The connection of hydrodynamic parameters is revealed. The hydrodynamic laws of the foam layer are considered. The indicated factors affecting the process of mass transfer, both in the gas and in the liquid phases. The conducted analysis of a number of studies showed that the perspective direction of intensification of the mass transfer process is the development of apparatuses with a three-phase fluidized bed of an irrigated nozzle of complex forms with mesh materials