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Spinal muscular atrophy (SMA) is a devastating childhood disease primarily affecting lower motoneurons in the spinal cord. SMA is caused by the loss of functional survival of motoneuron (SMN) protein, leading to structural and functional alterations of the cytoskeleton in motoneurons and other cells. Loss of SMN results in impairments of microtubule architecture, but the underlying mechanisms are not completely understood. In this study, we mechanistically analyzed the effects of SMN deficiency on microtubules, demonstrating a reduced stability together with a reduction in alpha tubulin detyrosination. This was caused by increased levels of microtubule-associated protein 1B and tubulin tyrosine ligase, resulting in mitochondrial mislocalization in SMA. Our findings suggest that altered tubulin post-translational modifications and microtubule-associated proteins are involved in the pathomechanisms of SMA, such as an impaired axonal transport of mitochondria.

Sustainability 12(11), 4369 (2020). doi:10.3390/su12114369 special issue: "Special issue "Performance-oriented integrative sustainability approaches to architecture, urban design and landscape architecture" / special issue editor: Michael Hensel, guest editor", Published by MDPI, Basel

Our take on questions of architecture and performance is rooted in a linked environmental and cultural ethic and endeavour. Its aim is to improve on the relation between architecture and environment, while basing this approach wherever possible on locally specific cultural practices. As construction impacts upon our planet at a momentous rate, consuming in the process vast amounts of resources in terms of surface area, material and energy and impacting massively on the bio-physical environment, we pose two related questions: (1) can architecture be in the service of the bio-physical environment; and, by extension, (2) can architecture principally be conceived of as not in conflict with, but rather as an embedded part of its local bio-physical environment? This chapter examines what this involves.

Moltke feldmareşal yani Alman ordusunda en yüksek rütbesine kadar yükselmiş bugün ki modernAlman ordusunun temellerini atan daha sonraları Almanya da genelkurmay başkanlığına getirilmiş19.yüzyılın en kıymetli komutanlarından birisidir. Kitabımız Moltke Paşa’nın 1836-1839 yıllarıarasında Osmanlı İmparatorluğun da askeri danışmanlık yaptığı dönem de aile ve dostlarına yazdığımektupların derlemesinden oluşmaktadır. Moltke Osmanlı imparatorluğun da kaldığı süre boyuncabirçok gözlemine bu eserinde yer vermiştir ancak askeri tarih çalışma niyetinde olan araştırmacılar içinmükemmel bir kaynak denilemez. Belirttiğim gibi bu eser mektupların derlenmesinden oluşmaktadırdaha çok bir hatırat tarzında içinde yüzeysel değerlendirmelerin bulunduğu daha çok Moltke'nin şahitolduğu olaylar üzerinden ilerler. Bu eser Alman genelkurmayına sunulmuş bir tahlil vedeğerlendirmeleri içeren bir rapor olsaydı çok daha içerik olarak faydalı olurdu buna rağmen anılandönemin sorunlarından haberdar bir araştırmacı Moltke’nin tarafsız aktarımlarından faydalanarakönemli değerlendirmelerde bulunabilir.

Günümüz terminolojisinde İmparatorluk kelimesi artık bir asır öncesinde kalmış devlet yapısını ifadeetmekten öteye gitmese de, içerisinde birçok din, etnik köken, dil gibi çeşitli unsurları barındıran buyapıdaki devletlerin ortadan kalkmasının ardından neredeyse yüzyıl geçmesine rağmen günümüzsiyasetinde ki etkileri birçok mecrada tartışılıp analiz ediliyor. Misal olarak Balkanlar’da 400 yıldan fazlahüküm sürmüş ve Balkan Savaşlarıyla birlikte büyük çöküşün başladığı Osmanlı İmparatorluğunun yerinialan Türkiye Cumhuriyetinin bugün Balkanlarda ki faaliyetleri, başta İsrail, Rusya ve Avrupa birliğindenözellikle Orta Avrupa ülkelerini rahatsız etmektedir. Bu konuyla ilgili uluslarası mecrada ‘Türkiye’ninBalkanlarda ki yumuşak gücü’ başlıklı birçok yazı bulabilirsiniz. Sonuçları bu kadar etkili olan bir hadiseyiiyi kavrayabilmek ve iyi analiz edebilmek için, nedenselliği doğru kurmak oldukça önemlidir. İşte tam bunoktada Norman Stone gibi deneyimli ve açık zihinli bir akademisyenin yazdığı bu kitap İmparatorluközgeçmişine sahip olan Türk okuyucusu için, akıcı dili ve sade anlatım biçimi ile çok iyi bir fırsattır.

Hyaluronic acid (HA) is a natural biopolymer and has long been attracting the attention of biotechnology industry due to its various biological functions. HA production with natural producer Streptococcus equi subsp. zooepidemicus has not been preferred because it has many drawbacks due to its pathogenicity. Therefore, in the present study, Streptococcal hyaluronan synthase gene (hasA) was introduced and expressed in Lactococcus lactis, through the auto inducible NICE system and the effect of nisin amount on the production of HA was examined. Newly constructed plasmid was transformed into L. lactis CES15, produced 6.09 g/l HA in static flask culture after three hours of induction period with initial 7.5 ng/ml nisin concentration within total six hours of incubation. The highest HA titer value ever was reported for recombinant HA-producing L. lactis by examining the effect of initial nisin concentration. We have shown that initial nisin concentration, which used to initiate the auto-inducing mechanism of NICE system and consequently hyaluronan synthase expression, has a direct and significant effect on the produced HA amount. Recently constructed recombinant L. lactis CES15 strain provide significant advantages for industrial HA production than those in literature in terms of production time, energy demand, carbon usage, and safety status.

Wnt signaling pathway is critically important in stem cell biology, both in homeostatic maintenance and regeneration of tissues and organs. Aberrant activation of this pathway has been described as a key player in the development of a wide array of tumor types, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are believed to be responsible for disease relapse, as they possess drug-resistance properties.The development of new therapeutic drugs targeting this pathway topromise new hope to eliminate CSCs and achieve cancer eradication. We review the Wnt signaling pathway, the relationship between this pathway and CSC term and recent therapeutic approaches to target this pathway and their clinical applications, Wnt sinyal yolağı kök hücre biyolojisinde, doku ve organ rejenerasyonunda ve homeostatik devamlılığın sağlanmasında kritik bir öneme sahiptir. Bu yolağın anormal aktivasyonunun pek çok tümör tipinin gelişiminde anahtar bir rol oynadığı ve bu durumun kanser kök hücrelerin (KKH, cancer stem cell=CSC) davranışını etkilediği bilinmektedir. KKH’ler ilaca direnç gösterebilme özelliğinden dolayı hastalıkların nüks etmesinin temel nedeni olduğu düşünülmektedir. Wnt sinyal yolağını hedef alan yeni terapötik ilaçların keşfedilmesi, KKH’lerin elimine edilmesine ve kanserin yok edilmesine yönelik yeni umutlar vaat etmektedir. Bu derleme de Wnt sinyal yolağı, bu yolağın kanser kök hücre kavramı ile ilişkisi ve klinik uygulamalarını hedef alan yakın zamandaki terapötik yaklaşımlar tartışılmıştır

It is an effective antioxidant molecule that exhibits free radical scavenging activity and it enhances antioxidant status in rats and exhibited anticancer properties. It has been shown that α-Lipoic acid is a very effective molecule against type 2 diabetes, atherosclerosis, inflammatory skin diseases, reperfusion arrhythmias and Parkinson’s disease and serves apoptotic action in different cancer cells. These molecules can display important roles in treatment of colon cancer. In this study, we examined the synergetic effects of α-lipoic acid and L-carnitine on HCT 116 +/+ and HCT 116 -/- colon cancer cell line. For this purpose, HCT 116 +/+ and -/- colon cancer cells were treated with L-carnitine and α-Lipoic acid for 24 hours and MTT assay and caspase 3 enzyme activity assay was conducted. α -Lipoic acid and L-carnitine alone or in combination decreased cell viability in HCT 116 +/+ and /- colon cancer cells and exhibited synergetic effect on the cell viability. Further studies must be conducted to find out the mechanism of their effects in cancer therapy, L-karnitin, uzun zincirli yağ asitlerinin mitokondri matriksine transportunda yer alarak, lipid metabolizmasında önemli görevlere sahip olan bir molekül olmasının yanı sıra, serbest radikal temizleyici aktivite gösterir ve antikanser özellikler sergiler. α-Lipoik asitin, tip2 diyabet, ateroskleroz, inflamatuar deri hastalıkları ve Parkinson hastalığına karşı oldukça etkili bir molekül olduğu gösterilmiştir ve farklı kanser hücrelerinde apoptotik etkiler gösterdiği bilinmektedir. Bu çalışmada, α-Lipoik asit ve L-Karnitin’in, HCT 116 +/+ ve HCT 116 -/- kolon kanseri hücre serilerindeki sinerjetik etkileri araştırılmıştır. Bu amaçla, HCT 116 +/+ ve -/- kolon kanseri hücreleri, L-karnitin ve α-Lipoik asit ile 24 saat muamele edildikten sonra, MTT testi ve kaspaz 3-enzim aktivitesi ile hücre canlılığı ve kaspaz-3 enzim aktivitesi üzerindeki etkileri incelenmiştir. Bu çalışmada, α-Lipoik asit ve Lkarnitin’in, kombinasyon halinde verildiklerinde sinerjetik etkiler sergileyerek, HCT 116 +/+ ve -/- kolon kanseri hücrelerinin canlılığını azalttıkları ve kaspaz-3 enzim aktivitesini artırdıkları görülmüştür. L-karnitin ve α-Lipoik asitin kanser terapisindeki sinerjetik etkilerinin mekanizmasını açığa çıkarmak için daha ileri çalışmalar yapılmalıdır

Architect Defne Sunguroglu Hensel and engineer Guillem Baraut Bover describe the Nested Catenaries design and construction system they have developed as part of a research project at the Oslo School of Architecture and Design (AHO). They explain how their innovative development of an unreinforced masonry shell structure made up of a single layer of bricks is informed by ancient building traditions and has been further evolved to be attuned to local context.

Hyaluronic acid (HA) is a natural biopolymer and has long been attracting the attention of biotechnology industry due to its various biological functions. HA production with natural producer Streptococcus equi subsp. zooepidemicus has not been preferred because it has many drawbacks due to its pathogenicity. Therefore, in the present study, Streptococcal hyaluronan synthase gene (hasA) was introduced and expressed in Lactococcus lactis, through the auto inducible NICE system and the effect of nisin amount on the production of HA was examined. Newly constructed plasmid was transformed into L. lactis CES15, produced 6.09 g/l HA in static flask culture after three hours of induction period with initial 7.5 ng/ml nisin concentration within total six hours of incubation. The highest HA titer value ever was reported for recombinant HA-producing L. lactis by examining the effect of initial nisin concentration. We have shown that initial nisin concentration, which used to initiate the auto-inducing mechanism of NICE system and consequently hyaluronan synthase expression, has a direct and significant effect on the produced HA amount. Recently constructed recombinant L. lactis CES15 strain provide significant advantages for industrial HA production than those in literature in terms of production time, energy demand, carbon usage, and safety status.

Infertility affects 1 in 6 couples and approximately 1 in 25 men. Male factor infertility is a major cause of spermatogenic anomalies, the causes of which are largely unknown. Impaired repro-ductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug re-sistance1 (MDR1) gene encodes a P-glycoprotein which has a role in the active transport of various substrates providing protection of somatic cells from potentially toxic substances, including xenobi-otics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular mac-rophages, and Sertoli cells. We performed genotype and haplotype analyses of MDR1 in 192 infertile and 102 fertile Turkish men for the genetic markers C1236T and C3435T, using polymerase chain reaction-restriction fragment length polymorphism analysis. In the overall population, correlations were analyzed in all genotype mod-els. We found that the C3435T polymorphism TT vs CT genotypes showed statistically significant differences in their association with infertility (P = 0.045), and that the CT genotype was associated with high sperm DNA damage (P = 0.02), suggesting that the CT genotype might be a susceptibility factor for infertility. Additionally, the T-T haplotype was significantly more frequent in the control group (13.2 vs 6.5%; odds ratio = 0.459, 95%CI = 0.259-0.814, P = 0.006). This study showed that MDR1 might have a role in male infertility. Fur-ther research in large cohorts with different populations is required to clarify the role of MDR in male fertility.

Nowadaysaccording to the increased prevalence of metabolic disorders such as diabetesand obesity, there is an increasing trend of consumption of non-caloric foodsand drinks. As a result of this situation there is a widely use of the extractsof a natural plant, Stevia rebaudiana, or its compounds as a sweetener. In thisstudy, it was aimed to investigate possible toxixological effects of stevia andits oxidative compounds on an oxidant parameter in liver tissue from rats.For this aim, 26adult Wistar type albino rat were used in the study. The animals were dividedinto two groups as the control group (n=10) and the study group (n=16)randomly. While the control group (Group 1) was fed only by standard rat diet,the study group (Group 2) was fed by standard rat diet with a sweetenerincluding 22 mg stevia extract per day aurogastricly for one month. At the endof the study, rats were sacrified and the liver tissues were surgically removedto analyze an oxidant parameter which is Malondialdehyde-MDA levels. And alsohistopathological examination and tissue DNA extraction were done.According to theresults of the study in liver tissues, MDA levels of the study group which werefed by stevia extract were found significantly higher than that in the controlgroup (p=0,021). The tissues of the group 2 displayed some histopathologicalchanges such as remarkable dilatation of sinusoids. There were nohistopathological changes in the structure of hepatocytes and also we did notobserve any apoptotic or necrotic cell and histopathological changes in theportal area, except the cellular infiltration in a few focal portal areas.There was no difference between groups according to DNA extraction findings.According thedata of MDA levels and histopathological findings, it was thought that theconsumption of high dose of stevia as a sweetener may cause oxidant effects onliver tissues.

Institute of ForensicSciences, Ankara University, Ankara, TurkeyDepartment of MedicalBiology, Ankara University Faculty of Medicine, Ankara, TurkeyAnkara Group Administrationof the Council of Forensic Medicine, Ankara, TurkeyDepartment ofBiochemistry, Ankara University Medical Faculty, Ankara, TurkeyPaintthinner is one of the cheapest member of volatile substances. A huge range ofhousehold and industrial products such as paint thinner, glue, lighter refills,gas, aerosols and solvents can be used as drug. Drug abuse including volatilesubstance abuse killed 200 000 people in 2014 according to UNODC-Word DrugReport 2015. Long-term volatile substances abuse as drugs can damage nervoussystem, liver, kidneys, brain, five sense organs, muscles and may cause suddensniffing death syndrome. In this study, we analyzed Bax and Bcl-2 expression inan adult male whose cause of death is paint thinner intoxication and comparedexpression level with postmortem control.

Acute myeloid leukemia is a type of clonal hematopoietic stem cell disorder displaying different genetic abnormalities. The critical balance between the self-renewal and differentiation of leukemia stem cells are regulated by various genes and signaling pathways that are regulated by these genes. Wnt/ β-catenin signaling pathway controls the self-renewal of hematopoietic stem cells by the regulation of β-catenin. Akirin-2 is an evolutionarily conserved nuclear protein which is thought to play important roles in immunity, NFκB and Wnt/β-catenin signaling pathways. In this study, expression of Akirin-2 gene was investigated in the CD34+ hematopoietic stem cells of patients with high β-catenin gene expression. Our results showed that the expression level of Akirin-2 gene was significantly higher in CD34+ hematopoietic stem cells of patients compared to healthy subjects and Akirin-2 gene could have an important role in AML pathogenesis, Akut miyeloid lösemi (AML), farklı genetik anomaliler gösteren bir grup klonal hematopoetik kök hücre bozukluğudur. Lösemik kök hücrelerin kendini yenileme ve farklılaşmaları arasındaki hassas dengeyi, çeşitli genler ve bu genlerin düzenlediği sinyal yolakları kontrol etmektedir. Wnt/β-katenin sinyal yolağı, β-kateninin regülasyonu aracılığıyla hematopoetik kök hücrelerin kendilerini yenilemelerini kontrol etmektedir. Akirin2 proteini ise, immünite, NFκB ve Wnt/β-katenin sinyal yolaklarında çok önemli rolleri olduğu düşünülen yüksek derecede korunmuşluk gösteren bir proteindir. Bu çalışmada β-katenin gen ekspresyonu yüksek olan AML hastalarının CD34+ hematopoetik kök hücrelerinde Akirin2 geninin ifadesi araştırılmıştır. Sonuç olarak Akirin2 gen ifadesinin AML hastalarının CD34+ hematopoetik kök hücrelerinde sağlıklı bireylere göre anlamlı derecede artmış olduğu tespit edilmiş ve Akirin2 geninin AML patogenezinde önemli rollerinin olabileceğine dair ilk veriler elde edilmiştir

Despite its extensive empire, Persia historically presented a challenging environment for the building of structures and infrastructure. The mountainous landscape of the Iranian plateaus has an arid or semi-arid climate with distinct seasonal variations and temperatures that fluctuated throughout the day. Despite this, water management and soil-fertilisation strategies and passive environmental modulation in architecture were all highly developed previous to the 19th century so as to be finely attuned to the local context, while also responding to the greater demands of a centralised empire. Here Michael Hensel, Defne Sunguroglu Hensel, Mehran Gharleghi and Salmaan Craig discuss and illustrate their detailed findings of the performance of historic structures. These include qanats (water canals), water cisterns, ice houses and pigeon houses as well as the seminal Khaju Bridge in Isfahan and the Boroujerdi's House in Kashan.

Aim:Apoptosis is a genetically programmed cell death mechanism which plays important roles in normal physiology such as tissue homeostasis regulation and pathophsiology of various diseases. iNOS enzyme activation and nitric oxide synthesis in various cell types as a defense mechanism against microbial and viral pathogens plays an important role in inflammatory and immune pathologies such as atherosclerosis, rheumatoid arthritis, diabetes, septic shock, multiple sclerosis and highly uncontrolled production of nitric oxide leads to cell death. Recently, glucosamine which is acclaimed to be beneficial for inflammatory disorders such as osteoarthritis is widely used clinically. There is limited information regarding the effect mechanisms of glucosamine on apoptosis of mainly immune cells, macrophages. In this study, effects of different concentrations of glucosamine were tested on LPS/IFNγ activated RAW 264.7 macrophages.Materials and methods:RAW 264.7 macrophage cell line was treated with or without glucosamine before LPS/IFNγ stimulation. Nitrite levels, cell viability, caspase-3 activity, mitochondria membrane potential and flow cytometric analysis with Annexin V-PI cell staining was performed.Results and discussion:Glucosamine inhibited nitrite levels, increased mitochondrial membrane potential, decreased caspase-3 enzyme activity significantly (p

In Turkey, there exists a rich tradition of auxiliary architecture that is supplementary to permanent domestic structures. In hot climates, it often provides essential shade, either as stand-alone shelter or as transitional spaces between the cool interior and the sun-exposed exterior. It is a history that offers great potential for innovative sustainable solutions that require little or no energy. Michael Hensel and Defne Sunguroglu Hensel describe the work that they have undertaken in this area through the Auxiliary Architectures: Membrane and Cable-Net Systems Workshop at the Izmir University of Economy. Copyright © 2010 John Wiley & Sons, Ltd.

Previous to the widespread adoption of air conditioning in the 20th century, which introduced a distinct differentiation between controlled interior space and the external environment, ‘a wealth of strategies’ were developed in Turkey to moderate the transition between inside and outside. There is much to learn from these no-energy and low-energy solutions to climate control. Here, Michael Hensel and Defne Sunguroglu Hensel describe the original research and special study they undertook of external vertical thresholds in an extended envelope when they gained special access to the 17th-century Yerevan Kiosk and Baghdad Kiosk in the Topkapi Palace in Istanbul. Copyright © 2010 John Wiley & Sons, Ltd.

Since the onset of cartography in the 18th century, the fixed datum line and the figure-ground have become the predominant means of measuring and planning the built environment. In the first of three articles on the subject of extended thresholds, Michael Hensel and Defne Sunguroglu Hensel challenge this reductionist convention. By taking Deleuze and his reading of nomadic ‘smooth’ space as a starting point, they look at alternative models provided by historic settlements in Turkey. These include: the neolithic settlement at Catalhoyuk in southern Anatolia; the medieval hillside town of Mardin in southern Turkey on the Syrian border; the carved spaces and cities of Cappadocia, such as Goreme; and underground cities such as Derinkuyu, also in central Turkey. Copyright © 2010 John Wiley & Sons, Ltd.

Hyaluronik asit, tıbbi ve endüstriyel alanlarda yaygın olarak kullanılan ve dünya genelinde önemli bir pazar payına sahip bir biyopolimerdir. Birçok yapısal, fizyolojik ve biyolojik fonksiyona sahip olan bu biyopolimer hemen hemen tüm dokuların fonksiyonel bileşenidir. Hyaluronik asit yüksek su tutma kapasitesi, immünojenik olmaması, yüksek biyouyumluluğu sebebi ile ortopedik uygulamalarda, kozmetik, medikal ve farmasötik gibi çeşitli alanlarda yaygın olarak kullanılmaktadır. Hyaluronik asit ticari olarak hayvansal dokular ve patojenik Streptococcus cinsi bakteriler olmak üzere iki temel kaynaktan elde edilmektedir. Ancak bu kaynaklardan elde edilen hyaluronik asitin çeşitli kontaminasyon riskleri içermesi ve alerjik reaksiyonlar meydana getirmesi nedeniyle alternatif kaynakların geliştirilmesi önem kazanmıştır.Bu çalışmada hyaluronik asit üreten alternatif rekombinant bir suş oluşturulması hedeflenmiştir. Patojenik Streptococcus equi subsp. zooepidemicus suşundan elde edilen hyaluronik asitin kontaminasyon riskinden kaçınmak için bu suşun hyaluronan sentaz enzimini kodlayan hasA geni, bir laktik asit bakterisi olan Lactococcus lactis'e aktarılmıştır ve Lactococcus lactis'in hyaluronik asit üreten rekombinant L. lactis CES15 olarak adlandırdığımız suş oluşturulmuştur. Bu kapsamda öncelikle Streptococcus equi subsp. zooepidemicus'un hasA geninin 5' ve 3' ucuna spesifik primerler kullanılarak amplifikasyonu gerçekleştirilmiştir. Amplifiye edilen gen bölgesi nisin kontrollü promotor sistemine sahip bir plazmid vektör olan pNZ8150'ye aktarılmıştır. Rekombinant Lactococcus lactis CES15 suşu nisin ile indüklenerek hyaluronan sentaz geninin ekspresyonu kontrol edilmiştir ve hyaluronik asit üretim yeteneği araştırılmıştır. Çalışmada 7,5 ng/ml nisin ile indüklenen rekombinant Lactococcus lactis CES15'in 3 saatlik indüksiyondan sonra, 2,9746 mg/ml gibi yüksek bir miktarla hyaluronik asit ürettiği belirlenmiştir. Bu yüksek sonuca sadece tek bir genin klonlanması ile ulaşılmıştır ve 3 saat indükleme süresi literatüre kıyasla oldukça kısadır. Hyaluronic acid that widely used in medical and industrial area and has a significant market share worldwide is a biopolymer. This biopolymer having many structural, physiological and biological functions is functional components of virtually all tissues. Hyaluronic acid because of high water holding capacity, lack immunogenic, the high biocompatibility characteristics, are widely used in various fieldssuch as in cosmetics, medical and pharmaceutical and orthopedic applications. Hyaluronic acid is commercially obtained from two main sources as animal tissues and pathogenic bacteria, Streptococcus genus. Alternative sources of production are also important because of hyaluronic acid which obtained from these sources including various risks of contamination and giving allergic reactions.In this study, it was targeted the creation of an alternative strain recombinant producinghyaluronic acid. To avoid the risk of contamination of hyaluronic acid enzyme encoding gene, hyaluronan synthase obtained from strain ofpathogenic Streptococcus equi subsp. zooepidemicushas been transferred with a lactic acid bacterium Lactococcus lactis and recombinant Lactococcus lactis strain CES15 strain was formed from Lactococcus lactis producing hyaluronic acid. In this context, the hasA gene 5 'and 3' end amplification of Streptococcus equi subsp. zooepidemicus was performed using specific primers. The amplified gene in a plasmid vector with a nisin-controlled promoter systems pNZ8150 has been transferred. The expression of hyaluronan synthase gene was controlled by induced recombinant strains of Lactococcus lactis nisin CES 15 and hyaluronic acid production capability was investigated. In this study, recombinant Lactococcuslactis CES15 with induced 7.5 ng/ml nisin was determined producing hyaluronic acid as 2.9746 mg/ml. 106

Phenotypic similarity between unrelated organisms, known as convergence, is a result of shared problems of adaptation to similar environments and limited ecological range. Their separate genetic histories imply a developmental route to biological innovation. Convergence as a model of evolutionary change has been applied to biological evolutionary reasoning and functional studies. We propose its application to biologically driven convergence for innovations in design. This route necessitates at least the comparability of architecture with biology on three levels: (1) evolutionary design reasoning (2) convergence of design solutions and (3) ecological niche concept. These combine in ArchiTRIZ, which is introduced as a derivative of TRIZ (a Russian system of inventive problem-solving) in architecture. We are building an ontology of convergence based on wood and ceramics on a ArchiTRIZ model framework called Material-Ontology [MatOnt]. As a computational design tool, MatOnt can activate systematic transfer of...

Acute Myeloblastic Leukemia (AML) is a disease characterized with disruption of normal hematopoietic growth and differentiation and accumulation of numerous abnormal unmatured myeloid cells. Epigenetic mechanisms, in particular DNA methylation and histon modifications, play a major role in the modulation of gene activity in cancer and cause acute leukemias. Epigenetic changes can reverse pharmacologically with demethylating agents which are in use as targeted therapy of hematological malignancies. Methylprednisolone(MP) has been used with short course and high dose for treating newly diagnosed children with AML. Methylprednisolone induces differentiation of myeloid leukemia cells to granulocytes and macrophages and induces apoptosis of myleoid leukemia cells. First, MTT test is performed for evaluating how different MP doses effect cell cytotoxicity in time dependent manner. Viability decreased with increasing MP doses both 24. And 48. hours. For these doses, apoptosis and differentiation determinations were done with flow cytometry analysis. Following this step, the high and effective dose for HL60 cells established as 5x10-3. For this dose, DNA isolation wass done. After isolation, methylation specific PCR analysis was performed for p15, ER, CDX2 and Bcl-2 genes. According to results, while p15 and Bcl-2 gene promoters are unmethylated, ER and CDX2 gene promoters are methylated. In conclusion, the methylation profiles of p15, CDX2, ER and Bcl-2 do not change after MP treatment.MP has apoptotic effect and differentiates myeloid blast cells but it does not effect DNA methylation. It is the first in the literature that demonstrates if methylprednisolone shows its effect with epigenetic pathway. In conclusion HL-60 cell line shows that MP doesn’t effect DNA methylation, Akut Myeloid Lösemi (AML), erken hematopoetik kök hücrelerde bir dizi genetik değişiklik sonucunda normal büyüme ve farklılaşmanın bozulması, kemik iliği ve periferik kanda çok sayıda anormal olgunlaşmamış myeloid hücrenin birikimi ile karakterize olan bir hastalıktır. Son yıllarda, löseminin oluşum sürecinde DNA metilasyonundaki ve histon modifikasyonlarındaki değişikliklerin etkili olduğu konusunda çalışmalar yapılmış ve AML ve demetile edici ajanlar hematolojik hastalıkların tedavisi için hedef olarak belirlenmiştir. Yüksek doz metilprednizolon yeni tanı almış pediatrik AML hastalarının tedavisinde kısa süreli uygulanmakta ve başarılı sonuçlar alınmaktadır. Sentetik bir glukokortikoid olan metilprednizolonun (MP) yüksek dozda, myeloid lösemi hücrelerinin granülositlere ve makrofajlara farklılaşmasını ve myeloid lösemi hücrelerde apoptozisi indüklediğine dair çalışmalar literatürde bulunmaktadır. Bizim çalışmamızda, AML hücre serisinde metilprednizolonun farklı dozlarda hücreler üzerindeki sitotoksisite düzeylerini saptamak amacıyla MTT yöntemi kullanıldı. MTT testi sonucu canlılığın anlamlı derecede azaldığı dozlarda 24. ve 48. saatlerde apoptozis ve farklılaşma analizleri akım sitometri ile yapıldı. Etken dozun 5x10-3 olarak bulundu ve bu etken dozun uygulandığı HL-60 hücreleri ve kontrol grubu hücrelerinden DNA izolasyonu yapılarak metilasyon analizlerine devam edildi. AML’de sıklıkla metile olduğu bildirilen p15, ER ve anormal ekspresyonu görülen BCL-2 ve CDX2 genlerinin HL-60 AML hücre serisinde steroid tedavisi öncesi ve sonrası metilasyonuna bakılarak, metilprednizolonun etkisini, epigenetik yolaktan gösterip göstermediğini araştırıldı. P15 geni promotoru ve BCL-2 geni promotoru metile bulunmamıştır. ER geni promotoru ve CDX2 geni promotoru ise metile bulunmuştur. MP uygulaması sonrası genlerin metilasyon profillerinde bir değişiklik saptanmamıştır. Çalışmamızda yüksek ve etken dozun hücreleri farklılaşmaya ve apoptozise götürdüğü ancak bunu epigenetik yolak mekanizmalarından biri olan DNA metilasyonu üzerinden yapmadığı saptandı

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2015, Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 2015, Bu tez çalışması, yine aynı öğrencinin lisans tezi olarak verdiği 'Sivriltilmiş(Tapered) kirişte Euler-Bernoulli ve Timoshenko çözümlerinin sıcaklık altında incelenmesi ve titreşim analizi' konusunun temeline dayanmaktadır. Çalışmada bahsedilen kiriş teorileri, kirişlerin mekaniğinin anlaşılmasını sağlayan temel denklemlerden oluşur. Bu çalışmada bu teorilerin yardımıyla kiriş yapıların doğal titreşim frekansının bulunması ve literatür sonuçlarıyla karşılaştırılması amaçlanmaktadır. Euler-Bernoulli, Rayleigh, Shear(kayma) ve Timoshenko kiriş teorileri bilinen en yaygın teorilerdir. Bu tez çalışmasında, en temel ve basit teori olan Euler-Bernoulli kiriş teorisi ile en kapsamlı kiriş teorisi olan Timoshenko kiriş teorisi genel hatlarıyla incelenip, formülleri verilip karşılaştırılmıştır. Bu detaylı anlatımlar sonucunda sistemlerin doğal frekansının hesaplanabildiği formüller çıkarılıp gösterilmiştir. Tez yazım aşamasında gelecek çalışmalara vesile olması amacıyla sonradan Shear(kayma) kiriş teorisi de konular arasına dahil edilmiştir. Yine aynı şekilde bu teori için de genel formüller verilip, doğal frekans hesabı anlatılmıştır. Daha sonrasında bu kiriş teorilerinin genel karşılaştırılmaları, artıları ve eksileri ayrı bir konu altında incelenmiştir. Titreşim konusu, tez çalışmasının bir nevi temeli olduğundan çalışmanın başında detaylı bir şekilde anlatılmıştır. Bu konu hakkındaki genel bilgilendirmeler yine tezde yer alan üç kiriş teorisi için yapılacak olan analitik hesaplamalara yön vermiştir. Bu çalışmadaki titreşimin türü serbest titreşim olacaktır. Bu tez çalışmasının asıl amacı bu anlatılanların sivriltilmiş ankastre kiriş için uygulanmasıdır. Bununla beraber bu tarz kirişin temelinin düz ankastre kiriş olması sebebiyle bu kiriş tipleri de detaylı bir şekilde anlatılmıştır. Düz ankastre kiriş hakkında literatürde oldukça fazla çalışma vardır, bu durum tez çalışması için sonuç kısmında oldukça işe yaramıştır. Gelecek çalışmalara yol göstermek amacıyla kirişlerde kullanılan analiz yöntemleri anlatılmıştır. Bu yöntemlerden çalışmanın analiz kısmında kullanılacak olan Sonlu Elemanlar Yöntemi(SEY) detaylı bir şekilde açıklanmıştır. Bununla beraber, bu konu altında hem düz ankastre hem de sivriltilmiş ankastre kiriş için doğal frekans hesabı yapılıp sonuca ulaşılmıştır. Bu konu altında elde edilen doğal frekans sonuçları Euler-Bernoulli kiriş teorisinden yararlanılarak ifade edilip tablo halinde verilmiştir. Aynı zamanda yer değiştirme hesaplamaları için çeşitli kuvvetlerin ve sıcaklık etkilerinin bu yöntem üzerinden nasıl ifade edilip sonuca ulaşılacağı anlatılmıştır. Sivriltilmiş ankastre kirişin formülleri ve boyutsuzlaştırılmaları detaylıca anlatılmıştır. Bu tip kiriş için literatürde olmayan bir kabul yapılıp Euler-Bernoulli kiriş teorisi için farklı sivrilik parametrelerine göre formüller çıkarılmıştır. Aynı kabuller Timoshenko ve Shear(Kayma) teorisinde de yapılmıştır. Tez çalışmasında kullanılacak olan paket programlar genel hatlarıyla anlatılmıştır. Literatürde sivriltilmiş ankastre kiriş hakkında çok fazla çalışma olmaması sebebiyle bu tarz kiriş için MSC/Patran ve MSC/Nastran paket programıyla analiz yapılması çok detaylı bir şekilde anlatılmıştır. Bunun amacı bu tarz kirişler için MSC/Patran programının nasıl uygulandığına dair kısa bir rehber(tutorial) oluşturmaktır. Sonuç bölümü oldukça kapsamlı oluşturulmaya çalışılmıştır. Euler-Bernoulli kiriş teorisi, Shear(kayma) kiriş teorisi, Timoshenko kiriş teorisi ve MSC/Nastran analizleri yapılmış, bu sonuçlar literatürde yapılan çalışmalarla karşılaştırılıp yorumlanmıştır. Aynı zamanda çalışma için belirlenen iki farklı malzemeye sahip ve iki farklı parametrelere sahip kirişler için bu işlemler yapılıp yorumlanmış, sonraki çalışmalar için temel oluşturulmuştur., Beam theories consist of equations that help people understand the mechanics of beam type structures. The studies on this subject has been started with the works of Euler and Bernoulli, resulting the most renowned beam theory, Euler-Bernoulli Theory, late 19th century. The most important and comprehensive beam theory is named after Russian scientist, Stephen Timoshenko in early 20th century. Different from Euler-Bernoulli Theory, it includes shear and rotary inertia effects. This master's thesis is based on graduation project of "Investigation of Euler-Bernoulli and Timoshenko solutions of a tapered beam under thermal loads and free vibration analysis" which is also graduation project of same student. In this study, the beam theories consist of basic beam equations which provide an understanding for mechanics of beams. In this thesis, it is aimed to find natural frequencies of tapered beams with considered beam theories and their comparions with literature results. Euler-Bernoulli, Rayleigh, Shear and Timoshenko beam theories are the most common beam theories for analyzing the beam type structures. Most basic and simple theory, Euler-Bernoulli, and most detailed theory, Timoshenko, have been investigated in general, equations are provided and compared. As a result of these detailed examinations, the equations which make it possible to calculate natural frequencies are derived. During the study, in order to enlighten the next possible studies, Shear beam theory is also included and taken into account. In the same way, for Shear beam theory, general equations are provided and natural frequency calculations are explained. Afterwards, the comparisons of these beam theories are made and their pros and cons are investigated in a chapter. In this chapter, pros and cons of the shear theories have been tabulated to provide a better understanding for people to see the comparison. Besides, derivation of vibration equations and logic have been extensively mentioned in related sections for all the beam theories mentioned in this study. Their history, easiness and rate of employment have been explained. The calculation of the natural frequencies of the beam due to torsion have been explained in Euler-Bernoulli section, however, this application is not given among the results and discussion chapter. Vibration subject is told profoundly since it is the fundamental subject of this thesis study. Under vibration chapter, definition and classification of vibration, resonance phenomena are briefly explained. Especially, degrees of freedom is investigated deeply and several examples are provided. General information about the subject is provided for three different beam theories and their analytic solutions are mentioned. In this study, free vibration is chosen as the main subject since no external force is considered. Even though, there is no external force, the study has an utmost importance due to presentation of preliminary results for forced vibration, natural frequencies. The main goal of this thesis study is to apply these theories on a clamped beam. The beam is chosen is clamped since it has more application field than other support types in industry and it is more difficult to determine natural frequencies resulting from bending. In addition, these kinds of beams are regular beams and also they are explained in a detailed way. There are many studies in literature which comes in handy at the end of the thesis, comparing the results. Even though, the analyses are conducted with a software, MSC/Nastran, the employed finite element method is tried to be explained. In order to guide the future studies, utilized analyses methods for beams are recounted. From these methods, Finite Element Method (FEM) which is employed to analyze the structure is investigated and explained. This method is investigated deeply and the history is narrated. Using FEM, the natural frequency results are obtained for both regular clamped beams and tapered clamped beams. Implementation of finite element method to other support types apart from clamped support, is also mentioned. Obtained natural frequency results are expressed in Euler-Bernoulli beam theory results and tabulated. Moreover, for displacement calculations the effects of various forces and thermal loads and how they are going to be employed using FEM is mentioned. Tapered clamped beams are basically mentioned. Their cross section varies with length of the beam. As a result, varying cross section changes the area and moment of inertia, making it harder to solve the equations. The equations of tapered clamped beam and their nondimensionalizations are given profoundly. For these kinds of beams, some assumptions have been taken into account which does not exist in previous studies and different taper parameters are obtained. Using Euler-Bernoulli beam theory, this type of beams' natural frequency due to bending have been calculated and first eight modes have been tabulated for natural frequency values. Same assumptions are used in Timoshenko and Shear beam theories. In the continuous sections, how these kinds of approaches are applied is explained. For the employed software, another section has been created and they are introduced. Their application fields are investigated and some screenshots from software are provided in order to extend the coverage of the study. It is tried to supply enough knowledge for one to achieve free vibration analysis for beams. The analysis software is explained generally. Since there is no study for tapered beams in literature, MSC/Patran and MSC/Nastran software and how analyses can be conducted with them are explained in a very detailed way. This study has been done in order to create a simple tutorial for MSC/Patran software. All the screenshots starting from modeling to analyses have been provided. Afterwards, first eight mode shapes of the beam are also given by screenshots. The results chapter is tried to be composed as comprehensive as possible. Analyses were conducted with Euler-Bernoulli Beam Theory, Shear Beam Theory, Timoshenko Beam Theory, as well as MSC/Nastran software. Obtained results are compared with the results provided in the previous studies and interpreted. Furthermore, same processes are made for two different beams with two different materials providing a basis for future possible studies. In results section, eleven different beam configurations are taken into account. Seven of these are chosen from reference studies while remaining four are considered in order to extend the tables. Each of these configurations, all the results with different beam theories have been tabulated and output of analyses are given. Additionally, error functions are also plotted and discussed. Eventually, future studies are also mentioned in the results and discussion chapter. As future studies, it planned to extend the work to be applicable different boundary conditions, support types. Also as a solution method, differential transform method (DTM) can be used and compared with the other results., Yüksek Lisans, M.Sc.

The aim of this study was to determine the serum adenosine deaminase ( ADA ) levels in patients with brucellosis and compare them with the results of healthy individuals. Forty- eight subject were enrolled in this study : 34 patients with brucellosis and 14 healthy individuals. Serum ADA activity was assessed by spectrophotometer in patients with brucellosis and statistically compared with that of healthy individuals. A normal range of serum ADA was considered 5-35 IU/l. Serum ADA levels were also compared with Brucella agglutinations titers and serum C reactive protein (CRP). Serum ADA levels were found to be significantly higher in patients with brucellosis than in healthy individuals (43.45 ± 24.19 IU/l and 27.5 ± 9.3 IU/l, respectively) (P < 0.01). Serum ADA activity did not show any correlation between the Brucella agglutination titer and CRP level. Serum ADA level showed significant alterations in patients with brucellosis compared to healthy subjects. We concluded that serum ADA level may be used in the follow up of patients with brucellosis together with clinical and other laboratory findings.

To investigate the possible effects of aqueous garlic extract on the oxidant/antioxidant status and apoptosis in 32D (wild type mouse myeloid cell = normal) and 32Dp210 (BCR-ABL fusion gene (+) mouse myeloid cell = Chronic Myelocytic Leukemia cells) cell lines. Materials and methods: Aqueous garlic extract (10% w/v) was added into the cell line media with 2 different final concentrations (0.4% and 1%). At 0 h and at 24, 48, and 72 h later, the oxidant (malondialdehyde (MDA) level, and xanthine oxidase (XO) enzyme activity) and antioxidant (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities) parameters were measured in the cell lines. Results: It was observed that the garlic extract caused no change in the XO and antioxidant enzyme activities, but it increased the MDA level in the 32D cell line. However, significant increases were found in the MDA level, XO, and antioxidant enzyme activities in the 32Dp210 cell line treated by the garlic extract. Additionally, it was shown that garlic extract had antiproliferative and apoptotic effects on both cell lines. The most effective apoptotic dose was found to be 0.4% (w/v), and at this concentration the death risk of the 32Dp210 cell line was calculated at 2.08 times higher than that of the 32D cell line. Conclusion: It has been suggested that garlic directly causes oxidant stress in the 32D cell line owing to its own oxidant ingredients, and that the oxidant stress created by garlic in the 32Dp210 cell line might occur through increased XO activity and/or its oxidant ingredients. Additionally, antioxidant enzyme activities were found to increase in the 32Dp210 cell line; it would seem that this compensatory change could not prevent the oxidant stress created. We think that the oxidant potential of garlic extract might play a part in its possible anticancer potential, previously supposed by several investigators.

Amaç: Alzheimer hastalığı (AH) kişinin hafıza ve bilişsel becerilerini, hatta en sonunda en basit görevleri yapma becerisini bile yavaş yavaş bozabilecek geri dönüşümsüz ve ilerleyici bir beyin hastalığıdır. AHnın başlaması ve ilerlemesi, az anlaşılmış kompleks bir süreçtir. Bu çalışmada AHda diyabetle ilişkili olduğu düşünülen, beyin fonksiyonlarının bozulması açısından risk teşkil eden muhtemel bazı mekanizmalar araştırılacaktır. Yöntem: U87 (insan primer glioblastoma) hücrelerinin Dulbeccos modifiye Eagles ortamında kültürü yapıldı. Hücreler 48 saat süre ile insülin (10 ?g/ml), düşük miktar glukoz (11 mM, 2 mg/ml) ve yüksek miktar glukoza (55 mM, 10 mg/ml) maruz bırakıldı. Daha sonra harvest işlemi yapılarak protein izolasyonu gerçekleştirildi. Western blot membranları ve özel bir program ile primer anti-ADAMTS5, anti-IL-33, anti-NF?B, ve anti-GAPDH antikorları kullanılarak ilgili proteinlerin bantlarının tayini yapıldı ve bunların dansiteleri ölçülerek gruplar birbiri ile karşılaştırıldı. Bulgular: Western blot sonuçları insülin uygulanan U87 hücrelerinde ADAMTS5 proteininin azaldığını gösterdi. Düşük miktar glukoz uygulanması hücrelerde ADAMTS5 düzeylerinde orta derecede bir artışa yol açarken yüksek miktar glukoz uygulanması belirgin bir artışa yol açtı. Yüksek miktar glukoz uygulanan hücrelerde IL-33 protein düzeyinde açık bir indüksiyon tespit edilirken düşük miktar glukoz uygulanan grupta orta düzeyde bir azalma bulundu. İnsülin uygulanması ise IL-33 düzeyinde azalmaya neden oldu. NF?B ile immün reaksiyon veren antikorla yapılan muamelede insülin uygulanan hücrelerde NF?B protein düzeyinde keskin bir düşüş bulunurken düşük miktar ve yüksek miktar glukoz verilen gruplarda orta düzeyde bir azalma tespit edildi. Sonuç: Bu çalışma, U87 hücrelerinde aynı deneysel düzenek ile hem agrekanazlar hem de inflamasyon medyatörlerinin birlikte çalışıldığı ve sonuçlarının AH patofizyolojisiyle diyabet ve hipergliseminin birlikte yorumlanmaya çalışıldığı ilk çalışmadır. Çalışmanın sonuçları, insülin ve glukozun henüz bilinmeyen mekanizma(lar) ile ADAMTS, IL-33 ve NF?B sentezindeönemli fonksiyonlarıolabileceğini göstermektedir. Bütün agrekanazların ve diğer sınıf ADAMTS enzimlerinin yukarıdaki parametrelerle birlikte çalışılıp yorumlanacağı, ayrıca moleküler biyoloji, genetik, immunoloji ve diğer ilgili bilim dallarının ışığında AHda ADAMTS enzimleri ve inflamasyon medyatörlerinin patofizyolojiye katkılarının değerlendirileceği ileri çalışmalara ihtiyaç vardır., Objective: Alzheimers disease (AD) is a progressive and irreversible central nervous system disease, which slowly destroys cognitive skills and memory, and eventually even the ability to handle the simplest tasks. The initiation and progression of AD is a poorly understood complex process. Here, we have investigated possible biological mechanisms that could be responsible for the increased risk for diminished brain function associated with diabetes in AD. Method: The U87 cell line (human primary glioblastoma cell line) was cultured in Dulbeccos modified Eagles medium. Cells were incubated with insulin (10 μg/ml), low glucose (11 mM, 2 mg/ml) and high glucose (55 mM, 10 mg/ml) for 48 hours. Cells were harvested and protein isolations were performed. Primary anti-ADAMTS5, anti- IL-33, anti-NFκB, and anti-GAPDH antibodies were used to detect corresponding proteins and to measure band densities in Western membranes using a specific program. Results: Western blot analysis showed ADAMTS5 protein decreases in insulin-applied U87 cells. High glucose application led to a notable increase in ADAMTS5 levels in cells, while low glucose application caused a moderate increase in ADAMTS5 levels. An apparent induction of IL-33 protein was observed in high glucose-applied cells, while a moderate decrease was noted in the low-glucose applied group. Insulin administration led to a decrease in IL-33 levels. Immunoreaction of NFκB with corresponding antibody was found to be sharply decreased in insulin- applied cells while low and high glucose application led to a moderate decrease in NFκB. Conclusion: This is the first reported study that has investigated both aggrecanases and inflammation mediators in the same experimental setup with U87 cells and interpreted the results in the various aspects of AD pathophysiology related to diabetes and hyperglycemia. Our findings suggest that insulin and glucose may have important functions in the synthesis of ADAMTS, IL-33, and NFκB through undefined mechanism(s). Further investigations dealing with all aggrecanases and other class of ADAMTS enzymes should be carried out together with the above-mentioned parameters with the collaboration of molecular biology, genetics, immunology, and other related disciplines in order to elaborate the pathophysiological importance of ADAMTS enzymes and inflammation mediators in AD.

A survey in the year 2007 among medical students of Ankara University Medical School to assess the smoking rates showed that 25.1 % of them were smoking. Moreover, the smoking rate was 35 % at sixth grade students and 60 % of the smokers specified that they started smoking at medical school. This report provides a successful approach to decrease smoking among medical students by measures against starting smoking. An “Antismoking Group” composed of voluntary academic staff, nurses, students, psychologists, and a social worker of the medical school was established to engage in lowering the smoking rate and eliminating it eventually among our students. Several methods including regular monthly meetings, annual “Smoking or Health” symposiums, and lectures to first, second, and third grade students to increase their awareness related to harms of smoking and their role in the fight against smoking were carried out. Our surveys in the years 2009 (641 students) and 2012 (975 students) showed that total smoking rates dropped to 15.0 and 11.0 %, respectively (p < 0.0002). Moreover, the smoking rate for the sixth grade students dropped from 35.0 % in 2007 to 21.8 and 8.8 % in the years 2009 and 2012, respectively (p < 0.0002). In 2012, the smoking rates of first year and sixth year students were 7.8 and 9.0 %, respectively. These close rates of smoking at the first and last years of medical school training and the significant drop in smoking rates in 5 years confirm that our group pursued a realistic and successful strategy against smoking.

Glutathione S-transferases (GSTs) are phase II enzymes that detoxify hazardous xenobiotics including carcinogens. Inter-individual variations in GSTM1 and GSTT1 loci have been associated with several types of cancer, including leukemias. In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case-control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1(-)) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1(-)) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1(-) genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08-6.00; P0.0001]. Individuals with the GSTM1(-) genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69-1.80; P = 0.714]. The combined GSTM1(-)/GSTT1(-) genotype was significantly associated with risk of CML compared to the GSTM1(+) /GSTT1(+) genotype which was most frequent in both cases and controls [OR: 9.47; 95% CI: 3.61-24.87]. Similar findings have only been obtained in Turkish and Indian populations but not elsewhere. The GSTM1(+) /GSTT1(-) genotype was associated with a 2.5-fold increased risk compared with the GSTM1(-)/GSTT1(+) genotype, the second most frequent genotype (OR; 2.46; 95% CI: 1.17, 5.20), suggesting a complex interaction between GSTM1 and GSTT1. Our results indicate an association between the GSTT1(-) genotype, either alone or in combination with GSTM1(-) genotype, and risk of CML, suggesting a possible interaction between GSTM1 and GSTT1. These findings, which are possibly restricted to Turkey and India, warrant further research.

Plant-based diet supplements help the prevention and therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects and oxidant/antioxidant status of aqueous and ethanol extracts of wheatgrass were tested in human chronic myeloid leukemia CML (K562) cell line. Materials and methods: K562 cell lines were treated with 10% (w/v) concentration of aqueous and ethanol wheatgrass extracts. Cytotoxicity and apoptosis were determined morphologically and by MTT and DNA laddering. MDA level and CAT, SOD, and ADA activities of the cell lines were measured. Results: Both preparations inhibited the growth of leukemia cells in a time-dependent manner. The most apoptotic and antiproliferative effect was seen in the cell line treated with aqueous extract at 48 h (P < 0.001). Increases in MDA level and CAT and SOD activities were observed. Conclusion: Wheatgrass extract has an antioxidant activity, inhibits proliferation of leukemia cells, and induces apoptosis; thus, this finding may represent a novel therapeutic approach for the treatment of CML.