Application of 3D MAPs pipeline identifies the morphological sequence chondrocytes undergo and the regulatory role of GDF5 in this process

The activity of epiphyseal growth plates, which drives long bone elongation, depends on extensive changes in chondrocyte size and shape during differentiation. Here, we develop a pipeline called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which combines light-sheet microscopy, segmentation algorithms and 3D morphometric analysis to characterize morphogenetic cellular behaviors while maintaining the spatial context of the growth plate. Using 3D MAPs, we create a 3D image database of hundreds of thousands of chondrocytes. Analysis reveals broad repertoire of morphological changes, growth strategies and cell organizations during differentiation. Moreover, identifying a reduction in Smad 1/5/9 activity together with multiple abnormalities in cell growth, shape and organization provides an explanation for the shortening of Gdf5 KO tibias. Overall, our findings provide insight into the morphological sequence that chondrocytes undergo during differentiation and highlight the ability of 3D MAPs to uncover cellular mechanisms that may regulate this process

European energy security and the role of LNG

Thesis (M.A.)--Özyeğin University, Graduate School of Social Sciences, Department of Institute of Social Sciences Department of Public Law, 2017.İşbu çalışmanın amacı, hukuki açıdan Avrupa Birliği'nde enerji güvenliğinin nasıl algılandığı ve sıvılaştırılmış doğal gaz yani (dilimize geçtiği hali ile) LNG'nin bunu nasıl desteklediğinin açıklanmasıdır. Çalışma, enerjinin modern dünyadaki yerini, Avrupa'nın enerji güvenliği konseptini doğal gaz ve özellikle LNG kapsamında ne şekilde anladığı kapsamında değerlendirerek izah eder. Enerji güvenliğinin gerekliliği, hukuki bir bakış açısıyla ele alınmaktadır. Bahse konu konseptin hukuki açıdan anlaşılabilmesi, yalnızca hukukun tepkisiyle mümkündür ve Avrupa'nın enerji güvenliği konseptine bakış açısının analizine destek olmak için hukuki düzenlemeler ve somut vakalar örnek olarak kullanılmaktadır. Enerji güvenliğinin hukuki gelişiminin yanı sıra teknolojik gelişmeler de değerlendirilmekte ve bu açıdan LNG, enerji güvenliğine katkıları anlamında incelenmektedir. Çünkü, enerji olmaksızın ekonomi, hukuk olmaksızın enerji olmaz.The purpose of this work is to explain how energy security is perceived within the European Union and how liquified natural gas, in short LNG, supports it from legal aspect. This work states the place of energy in modern world by evaluating Europe's understanding of energy security concept under the scope of natural gas and especially LNG. The essentialness of energy security is discussed from a legal point of view. The aforesaid concept can only be understood by legal reactions and regulations and case studies are used as examples to support the analysis of Europe's energy security perception. Along with the legal development of energy security, technological development is also studied and LNG is discussed within the meaning of its reinforcement for the concept. Eventually, economy does not exist without energy; likewise energy does not exist without law

Transcriptional Regulation of Vascular Endothelial Growth Factor C by Oxidative and Thermal Stress Is Mediated by Lens Epithelium-Derived Growth Factor/p7512

Vascular endothelial growth factor C (VEGF-C) plays a critical role in tumor lymphangiogenesis and lymph node metastasis. We report here that VEGF-C expression is regulated by microenvironmental stress including hyperthermia and oxidative stress. Furthermore, we show that this stress response is mediated by transcriptional activation mediated by lens epithelium-derived growth factor (LEDGF/p75). Ectopic expression of LEDGF/p75 in C6 rat glioma and in H1299 human non-small cell lung carcinoma induced VEGF-C expression in vitro, whereas in subcutaneous mouse tumor xenografts, LEDGF/p75 stimulated VEGF-C expression and augmented angiogenesis and lymphangiogenesis. Conversely, overexpression of a LEDGF/p75 native antisense or LEDGF/p75-targeted short interfering RNA downmodulated VEGF-C expression. LEDGF seemed to conferred this activity on binding to a conserved stress response element (STRE) located in the VEGF-C gene because mutating the STRE was sufficient for the suppression of basal and stress-induced activations of the VEGF-C promoter. Thus, the study reported here identified a role for LEDGF/p75 in stress-regulated transcriptional control of VEGF-C expression. These results provide a possible link for LEDGF/p75 in tumor lymphangiogenesis and cancer metastasis. Hence, our data suggest the LEDGF-VEGF-C axis as a putative biomarker for the detection of stress-induced lymphangiogenesis and LEDGF as a potential target for antimetastatic therapy

Energy transport in dichromic metallo-organic crystals: selective inclusion of spatially-resolved arrays of donor and acceptor dyes in different nanochannels

In this study, the precise positioning and alignment of arrays of two different guest molecules in a crystalline host matrix has been engineered resulting in new optically-active materials. Sub-nm differences in the diameters of two types of 1D channels is sufficient for size-selective inclusion of dyes. Energy transport occurs between the arrays of different dyes that are included in parallel-positioned nanochannels by fluorescence resonance energy transfer (FRET). Dichromism and diattenuation of individual micro-sized crystals are dependent on their relative position under polarized light. This angular-dependent behavior is a result of the geometrically-constrained orientation of the dyes by the crystallographic packing of the host matrix and is concentration dependent. These functionalized crystals can find applications in optical switches and as bulk materials for light harvesting and up-conversion

The Hemodynamic Basis for Positional- and Inter-Fetal Dependent Effects in Dual Arterial Supply of Mouse Pregnancies

<div><p>In mammalian pregnancy, maternal cardiovascular adaptations must match the requirements of the growing fetus(es), and respond to physiologic and pathologic conditions. Such adaptations are particularly demanding for mammals bearing large-litter pregnancies, with their inherent conflict between the interests of each individual fetus and the welfare of the entire progeny. The mouse is the most common animal model used to study development and genetics, as well as pregnancy-related diseases. Previous studies suggested that in mice, maternal blood flow to the placentas occurs via a single arterial uterine loop generated by arterial-arterial anastomosis of the uterine artery to the uterine branch of the ovarian artery, resulting in counter bi-directional blood flow. However, we provide here experimental evidence that each placenta is actually supplied by two distinct arterial inputs stemming from the uterine artery and from the uterine branch of the ovarian artery, with position-dependent contribution of flow from each source. Moreover, we report significant positional- and inter-fetal dependent alteration of placental perfusion, which were detected by in vivo MRI and fluorescence imaging. Maternal blood flow to the placentas was dependent on litter size and was attenuated for placentas located centrally along the uterine horn. Distinctive apposing, inter-fetal hemodynamic effects of either reduced or elevated maternal blood flow, were measured for placenta of normal fetuses that are positioned adjacent to either pathological, or to hypovascular <em>Akt1</em>-deficient placentas, respectively. The results reported here underscore the critical importance of confounding local and systemic in utero effects on phenotype presentation, in general and in the setting of genetically modified mice. The unique robustness and plasticity of the uterine vasculature architecture, as reported in this study, can explain the ability to accommodate varying litter sizes, sustain large-litter pregnancies and overcome pathologic challenges. Remarkably, the dual arterial supply is evolutionary conserved in mammals bearing a single offspring, including primates.</p> </div

Assessment of the arterial blood supply to the placenta via BD-ASL MRI and intravital fluorescence microscopy.

<p>Two methods were used to explore the pattern of transfer of arterial blood to the placentas along the uterine horns in pregnant mice at late gestation (E17.5): 1) Bi-directional ASL methodology (Panels A–C); and 2) Intravital fluorescence microscopy imaging of the uterine arterial blood supply subsequent to intravenous administration of FITC-dextran to mice having undergone surgical arterial ligations of either the uterine branch of the ovarian artery, or the uterine artery (Panels D–F). (A–C) Placental saturation transfer maps obtained by BD-ASL MRI of an ICR pregnant mouse (E17.5). For placentas positioned closer to the cervix (Panel A: L1, R1), mainly negative BD-ASL contrast voxels (blue) were observed, consistent with the predominant contribution of maternal blood flow through the uterine artery. In placentas closer to the ovary (Panel C: L5–7), the BD-ASL contrast was mainly of positive voxels (red), implying that placentas in this part of the uterine horn are supplied through blood mainly from the uterine branch of the ovarian artery. Placentas located in the central region of the uterine horn (Panel B, L3–4) had a dispersive pattern of BD-ASL values with both negative and positive voxels, consistent with a dual supply from both the uterine artery and the uterine branch of the ovarian artery, respectively. (D) Intravital fluorescence microscopy image of the arterial blood supply to an intact uterine horn (a snapshot from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052273#pone.0052273.s003" target="_blank">Movie S1</a>). (E) Intravital fluorescence microscopy image of the arterial blood supply to a uterine horn following ligation of the uterine artery (a snapshot from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052273#pone.0052273.s004" target="_blank">Movie S2</a>). (F) Intravital fluorescence microscopy image of the arterial blood supply to a uterine horn following ligation of the uterine branch of the ovarian artery (a snapshot from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052273#pone.0052273.s005" target="_blank">Movie S3</a>).</p