Epigenetic regulation of SLIT-ROBO pathway in hepatocellular carcinoma

Ankara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2009.Thesis (Master's) -- Bilkent University, 2009.Includes bibliographical references leaves 44-50.Hepatocellular carcinoma is an aggressive, chemotherapy-resistant cancer and the prognosis of affected patients is very poor. Therefore, unraveling molecular components of hepatocarcinogenesis not only leads to the improvement of diagnostic and prognostic tools but also may reveal novel therapeutic targets. We previously defined the differential expression of SLIT-ROBO genes in HCC. To explore the mechanisms of the inactivation of these genes, we analyzed the hypermetylation of SLIT1, SLIT2, ROBO2 and ROBO3 genes in a group of HCC cell lines consisting of four high-AFP expressing well-differentiated (HUH7, Hep3B, PLC/PRF5 and HepG2) and low-AFP expressing poorly-differentiated cell lines (Focus, SKHep1, Snu387 and Snu423). We first demonstrated that the transcription of all studied genes can be rescued upon treatment of cell lines with 5-Aza-2‟-deoxycytidine (5- Aza-dC). Next, we analyzed the methylation of SLIT-ROBO genes by methylation specific PCR. All genes were found to be at least partially methylated, except ROBO3, which displayed a heavily methylated pattern. in silico analyses of the 5‟ upstream sequence of ROBO2 gene revealed a putative promoter region, an enhancer in the first intron and a CpG island. Methylation –specific PCR amplification of ROBO2 by using primers selected from this CpG island supports the potential of this region as a gene regulatory site. Therefore, it is worthy to extend the methylation analyses of SLIT-ROBO pathway in HCC patients. Furthermore, mechanistic studies on ROBO3, which was shown to counteract the overexpressed ROBO1 effects may shed light into the role of ROBO3/ROBO1 axis and the potential of ROBO3 as a tumor suppressor gene in HCC.Semerci, FatihM.S

Konya Kent Merkezinin Şekillenmesinde İktidarın Sosyolojik Etkisi

Kentlerin şekillenmesinde birçok etkenin yanında iktidar ilişkisi de etkili olmaktadır. İktidar sahibi kişilerin politik ve ideolojik yaklaşımlarını yansıtma istekleri, kentsel mekân düzenlemeleri ve yapıları inşa etmede doğrudan müdahalelerini kolaylaştırmıştır. Konya kent merkezi de tarih boyunca farklı iktidarların ideolojik müdahaleleriyle şekillenmiştir. Birçok medeniyete ev sahipliği yaparak günümüze ulaşan Konya kent merkezinin iktidar ideolojisiyle oluşan simgesel değerini koruyor olması bu çalışma kapsamında örneklem alan olarak seçilmesini sağlamıştır. Çalışmada Konya kent merkezinin geçmişten günümüze dönemsel olarak iktidar ideolojisiyle nasıl şekillendiğini tespit etmek amaçlanmıştır. Konya kent merkezinin gelişimi ile alakalı literatür taranmış ve birçok çalışmaya ulaşılmıştır. Elde edilen verilere bakıldığında iktidar gücünün tarih boyunca kentsel alanların düzenlenmesinde etkili olduğu sonucuna varılmıştır. Konya özelinde ise Cumhuriyet öncesi dönemde hâkimiyet sahibi medeniyetlerin dini, askeri ve kültürel yaşam tarzları doğrultusunda doğrudan erk gücü ile kenti şekillendirdiği gözlenirken Cumhuriyet sonrası yaşanan rejim değişikliği ve sonrasında ortaya çıkan planlama kararları iktidarın kent üzerindeki etkisinin yasal boyutlara taşındığını göstermektedir

Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Altres ajuts: Cancer Prevention and Research Institute of Texas (CPRIT), Core Facility Support Award (CPRIT-RP180672, R1313, 1R01GM138781-01); NIH (CA125123, RR024574); Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (P50HD103555); BCM start-up funds; Albert and Margaret Alkek Foundation; McNair Medical Institute; Robert and Janice McNair Foundation; BCM Seed Funding (1P20CA221731-01A1); National Institute of General Medical Sciences (R01 GM120033); Cynthia and Antony Petrello Endowment; Mark A. Wallace Endowment; McKnight Foundation; Dana Foundation; BCM Computational and Integrative Biomedical Research Center seed grant.Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis

Syntheses, structure and spectral studies of a new highly luminescent Cd(II)-5-sulfoisophtlialate coordination polymer

A new coordination polymer, [Cd-2(mu(3)-sip)(2)(etim)(6)Cd(etim)(2)](n) (1) (sip = 5-sulfoisophtalate, etim = 2-ethylimidazole) has been synthesized and characterized by elemental analysis, spectral (FT-IR and photoluminescence) and thermal analysis. The structure of polynuclear complex 1 has been determined by the X-ray diffraction. Complexes 1 shows intense photoluminesent emission bands at 415 nm upon excitation at 319 nm. The emission of complex may be attributed to ligand centered luminescence emission. X-ray diffraction analysis of complex 1 reveals that it has a 1D polynuclear zig-zag chain. The 1D zig-zag chains in 1 are connected each other by N-H center dot center dot center dot O interaction and aromatic interaction between imidazole rings to form 3D supramolecular structure of 1.Kirklareli UniversityKirklareli University [KLUBAP-71]This work has been supported by the Kirklareli University (Project No. KLUBAP-71).WOS:0004526403000032-s2.0-8505350521

Effect of substituent groups on the structures of two semi-flexible bis(imidazole) directed Zn(II)-5-sulfoisophthalate coordination polymers: Syntheses, structures and photoluminescent properties

Two new metal organic architectures, formulated as {(pbetixH(2))(0.5)[Zn(mu-sip)(mu-pbetix)(0.5)]}(n) (1) and {[Zn-2(mu-sip)(2)(pbisopix)(pbisopixH)(2)]center dot 4H(2)O}(n) (2), were synthesized based on the rarely employed 1,4-bis((2-ethylimidazol-1-yl)methyl)benzene (pbetix) and 1,4-bis((2-isopropylimidazol-1-yl)methyl)benzene (pbisopix) ligands, along with the 5-sulfoisophthalate (sip) ligand. Complexes 1 and 2 were synthesized in basic medium and under mild hydrothermal conditions. Both complexes were characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray diffraction studies. Crystallographic studies of complexes 1 and 2 reveal that the Zn(II) ions are mu-bridged by trianionic sip(3-) ligands in the bis(monodentate) coordination mode to generate 1D polymer chains. In the complexes, adjacent chains are linked by the bis(imidazole) ligands to form a 2D structure. Complex 1 is the first example containing a protonated bis(imidazole) ligand, namely the pbetixH(2) cation, while complex 2 is the first example with a monoprotonated bis(imidazole) ligand, namely pbisopixH. Topological analyses of the 2D coordination polymers reveal that complex 1 is a 3-fold polycatenated 4-connected uninodal net with the point symbol of {4(4).6(2)}, whereas complex 2 is a 3-connected uninodal net with the point symbol of 63. The thermal behavior, photoluminescent properties and topological analysis of the complexes are also discussed herein. (C) 2017 Elsevier Ltd. All rights reserved.Kirklareli UniversityKirklareli University [KLUBAP-71]This work has been supported by Kirklareli University (project no: KLUBAP-71). Dr. Semerci acknowledges the Scientific and Technological Research Application and Research Center, Sinop University, Turkey for the use of the Bruker D8-QUEST diffractometer.WOS:0004194099000082-s2.0-8503202192

Syntheses and photoluminescence properties of new Zn(II) and Cd(II) coordination polymers prepared from 5-sulfoisophthalate ligand

New coordination polymers, formulated as {[Zn(µ-sipH)(µ-apim)]·3H2 O} n (1) and {[Cd(µ-sip)(H2 O) 2 (apimH)]·3H2 O} n (2) were synthesized based on the 1-(3-aminopropyl)imidazole (apim) along with 5-sulfoisophthalate (sip) ligands. The complexes were synthesized under mild hydrothermal conditions. All the complexes were characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray diffraction studies. The X-ray crystallographic studies of 1 and 2 reveal Zn(II) and Cd(II) ions are µ-bridged by dianionic sipH and trianionic sip ligands in bis(monodentate) and bis(bidentate) coordination mode, respectively, to generate 1D polymer chains. In complex 1, the adjacent chains are linked by two apim ligands to form a 1D nanotubular structure. Complex 2 is the first example of a protonated apimH ligand. In the complexes the adjacent 1D chains extend into a 3D supramolecular network by hydrogen bonds. The thermal decomposition behavior and photoluminescent property of the complexes are also discussed herein

A New Highly Thermally Stable Co(II)-coordination polymer with Semi-flexible Bis(Imidazole) Directed Secondary Building Unit: Solvothermal Syntheses and Structures

A new thermally highly stable 2D coordination polymer, formulated as [Co(μ6-aO2btc)0.5(μ-obix)]n (ao2btc = dioxygenated form of 3,3′,5,5′-azobenzenetetracarboxylate) synthesized using the semi-flexible 1,2-bis(imidazole-1-ylmethyl)benzene (obix) ligand in solvothermal conditions and characterized by single-crystal diffraction, FT-IR and photoluminescence spectroscopy and thermogravimetric/differential thermal analysis. Crystallographic studies of complex 1 reveal that two Co(II) ions are bridged by carboxylate groups of ao2btc ligand to form paddle-wheel SBU. These SBUs are stabilized by the coordination of obix ligand. The Co(II) ions are µ6-bridged by hexadentate aO2btc ligand to generate 2D polymer chains with 3,4-connected binodal net (point symbol {4.62}2{42.62.82}) and topological type is 3,4L13. Thermal analysis shows that complex 1 thermally stable up to 401 °C

Synthesis, Characterization and Structural Investigations of Two New Cu(II)-Pyridine-3,4-dicarboxylate Complexes

Bu çalışmada piridin-3,4-dikarboksilik asit (3,4-pydcH2 ) ve diamin türevi 1,2-diaminoetan (en) ve 1,3- diaminopropan (pen) ligantları kullanılarak karışık ligantlı [Cu(3,4-pydc)(en)2 ]∙2H2O (1) kompleksi ve {[Cu(3,4-pydc)(pen)2 ][Cu(µ-3,4-pydc)(pen)2 ]∙H2O}n (2) koordinasyon polimeri sentezlendi ve yapıları, elementel analiz, FT-IR spektroskopisi, UV-Vis spektroskopisi, termal analiz (TG/DTA) ve X-ışınları tek kristal çalışmaları ile aydınlatıldı. X-ışını tek kristal analizi çalışmaları sentezlenen 1 kompleksinin mononükleer, 2 kompleksinin yapısında ise hem mononükleer hem de 1D polinükleer yapının bulunduğunu göstermektedir. 3,4-pydc ligantı 1 kompleksinde tek dişli ligant olarak davranarak azot atomundan Cu(II) iyonuna koordine olmuştur. 2 kompleksinde ise mononükleer birimde azot atomundan tek dişli olarak, polinükleer birimde ise hem azot hem de karboksilat oksijen atomundan Cu(II) iyonlarını arasında köprü ligant özelliği sergilemektedir. Komplekslerin 3D supramoleküler yapıları, N–H∙∙∙O ve O–H∙∙∙O tipi hidrojen bağları etkileşimleri sayesinde oluşmaktadır.In this study, new two Cu(II)-pyridine-3,4-dicarboxylate (3,4-pydc) complexes with 1,2-diaminoethane (en) and 1,3-diaminopropane (pen), Cu(3,4-pydc)(en)2 ]∙2H2O (1) and {[Cu(3,4-pydc)(pen)2 ][Cu(µ-3,4- pydc)(pen)2 ]∙H2O}n (2) have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, UV–Vis. spectroscopy, thermal analysis and single crystal X-ray diffraction studies. The molecular structures of mononuclear 1 and both mono and polynuclear 2 complexes have been determined by the single crystal X-ray diffraction. In complex 1, Cu(II) ion was coordinated by 3,4-pydc ligand with its nitrogen atom in a monodentate manner. In complex 2, both Cu(II) ion was coordinated by 3,4-pydc ligand with its nitrogen atom in a monodentate manner and Cu(II) ion was coordinated by 3,4-pydc ligand with its nitrogen and oxygen atoms in a bidentate manner which exhibit bridged ligand. 3D supramolecular structures of complexes consist of N–H∙∙∙O and O–H∙∙∙O type hydrogen bonding interactions

Two-Dimensional Metal-Organic Framework Nanostructures Based on 4,4 '-Sulfonyldibenzoate for Photocatalytic Degradation of Organic Dyes

Four new two-dimensional metal-organic frameworks, namely, [Zn-2(sdba)(2)(pbisopix)](n) (KLU-8) (KLU is referring to Kirklareli University), {[Cd-2(sdba)(2)(pbisopix)]center dot 2H(2)O}(n) (KLU-9), [Cd(sdba)(pbisopix)](n) (KLU-10), and [Cd-(sdba)(pbetix)](n) (KLU-11) have been synthesized using a V-shaped 4,4'-sulfonyldicarboxylic acid (H(2)sdba) as anionic and 1,4-bis((2-isopropylimidazol-1-yl)methyl)benzene (pbisopix) or 1,4-bis((2-ethylimidazol-1-yl)methyl) benzene (pbetix) as neutral ligands and characterized by various techniques. In KLU-8 and KLU-9, the {M-2(CO2)(4)} secondary building units (SBUs) are connected by sdba(2-), while in KLU-10 and KLU-11 Cd(II) ions bridged by sdba(2-) form a 2D structure of MOFs revealed by single crystal X-ray diffraction analyses. The topology of MOFs is found to be a 2D sql network. The synthesized MOFs are stable in aqueous medium up to 7 days. KLU-10 and KLU-11 were well-exfoliated via facile sonication process in 10 min, at room temperature, whereas, KLU-8 and KLU-9 showed poor exfoliation yield because of their interpenetrated structure according to the FESEM images. Furthermore, the surface area measurement also proved the exfoliation of MOFs; that is, the exfoliated samples exhibited higher surface area than that of bulk counterparts. The photocatalytic properties of exfoliated MOF nanostructures in the photodegradation of three organic dyes (methyl orange (MO), methylene blue (MB), and rhodamine B (RhB)) have been investigated under UV/vis irradiation. The photodegradation efficiencies of MO, MB, and RhB can reach almost 100% within 40 min, 59% within 60 min, and 66% within 60 min, respectively in the presence of MOF nanostructures as photocatalyst and molecular oxygen as oxidant. The superior photocatalytic efficiency toward MO degradation of KLU-10 and KLU-11, might be attributed to the very high exfoliation yields of MOFs.Scientific Research Fund of Kirklareli University, Turkey [KLUBAP-197]We thank Dr. Mursel Arici for the DR/UV measurement and band gap calculation. We also thank Dr. Patrick Whitty for proofreading the manuscript. We acknowledge Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer. This work was supported by the Scientific Research Fund of Kirklareli University, Turkey (Project No. KLUBAP-197)

Synthesis and characterization of new Ag(I) coordination networks based on saccharinate and bis(isopropylimidazole) ligands exhibiting very close C-H...Ag interactions

Two Ag(l) coordination networks, formulated as [Ag(sac)(mu-bisopib)](n) (1) and [Ag(sac)(mu-pbisopix)].H2O (2), have been synthesized based on the bis(isopropylimidazole) ligands 1,4-bis(2-isopropyl-1H-imidazol-1-yl)butane (bisopib) and 1,4-bis((2-isopropyl-1H-imidazol-1-yl)methyl)benzene (pbisopix), respectively, along with saccharinate (sac) ligands. All the complexes were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction studies. The X-ray crystallographic studies of 1 and 2 revealed that the Ag(I) ions are mu-bridged by the bis(isopropylimidazole) derivative ligands to generate 1D zig-zag polymer and dinuclear structures, respectively. As far as we know, complex I shows the closest C-H...Ag interaction distance among similar literature examples. In complex 1 adjacent 1D coordination polymers are further joined by C-H...O hydrogen bonds and pi...pi interactions, generating a 3D supramolecular network. The C-H...O hydrogen bonds and C-H...pi interactions play a crucial role in the architecture of the 3D network of complex 2. Thermal decompositions and photoluminescent properties of the Ag(I) complexes are also discussed herein. (C) 2016 Elsevier Ltd. All rights reserved.WOS:0003940633000362-s2.0-8500818779