Cornea is the transparent outermost layer of the eye. It is a thin (500 &micro / m) multilayer tissue which performes around 75% of the total refraction in the eye. It also protects the inner layers against any type of damage. Since it is avascular, the three cellular layers of cornea always need transport of nutrients and other materials in and out of the tissue via diffusion. Any change in shape, transparency or thickness of cornea, or physical damages and infections, may cause serious defects. The conventional methods are satisfactory in the treatment of mild injuries but severe cases require the substitution of the tissue with an equivalent. Keratoprosthesis and donor corneas that are used as replacements do not completely meet requirements. Tissue engineering can be an alternative method for preparing a biocompatible and stable cornea equivalent. The ability to choose from a variety of materials and the ability to incorporate bioactive agents allow the researchers to tailor make the construct. The structure needs to be seeded with the patient&rsquo / s own cells and cultured in vitro to yield an optimal corneal replacement. In this study a novel, split thickness cornea replacement is proposed to substitute the two upper cellular layers (epithelium and stroma) of the native cornea. The design includes a chondroitin sulfate impregnated collagen type I (isolated from rat tail) foam (CSXLF) produced by lyophilization carrying electrospun fibers of the same polymer collected directly on top of the foam, forming the bilayer structure (Fo-Fi). The fiber layer was intended to separate the epithelium and the stroma of the reconstructed cornea yet to allow material transfer in between. The foam layer (bottom) was crosslinked by N-ethyl-N-[3-dimethylaminopropyl] carbodiimide (EDC), and N-hydroxy succinimide and after fiber deposition the bilayer was further stabilized with physical crosslinking (DHT method). The physical characterization of the foam showed that their pore sizes (10-200 &micro / m) and porosities (around 70%) were well within the desired range for typical tissue engineering applications. The cell free wet thicknesses of both single and bilayer constructs were close to that of the native stroma and light transmittance through these scaffolds was quite high (around 82% in the 500-700 nm range). The scaffolds were also tested for their stability and shown to be suitable for in vitro testing. In vitro studies were performed using retinal pigment epithelial cells (RPE, D407 cell line) and isolated human corneal keratocytes (HK) to reconstruct the epithelium and the stroma, respectively. Three types of constructs were prepared / only HK seeded Fo-Fi constructs, RPE-HK seeded CSXLFs, and RPE-HK seeded Fo-Fi constructs. All were shown to support cell attachment and promoted cell proliferation as was shown by the cells that covered the inner and outer spaces of the scaffolds. The fiber layer prevented the mixing of the two cell types, without hindering material exchange between them. Moreover, when co-cultured for 14 days, the keratocytes started to deposit collagen type I, a specific marker of these cells. In contrast, ECM deposition could not be observed in the single type cell seeded samples. The co-cultured bilayer construct was tested for suturability at the end of 31 days of in vitro incubation and it was shown that it could be successfully sutured without any major tears. Under the light of these results it was concluded that both the single layer and the bilayer constructs show promise for use as split thickness cornea replacements.

NMDA (N-methyl D-aspartate) Receptor is a ligand and voltage gated ion channel and involved in many processes such as synaptic plasticity, memory formation, behavioral responses and cell survival. In the sense of functional activity, cellular localization of NMDAR is important since this receptor shows its activity on the membrane. Although NMDA receptor is intensely studied there are no satisfying study showing its localization with microscobic methods. Besides, the effect of florescent protein labelling of NMDA receptor on its distribution is not shown. It is expected to provide basis for further interaction and distribution studies with this comparison. Contrary to literature, in this study it is shown that NMDA receptor does not localize only in ER and membrane instead has a cytosolic pattern and this pattern is compatible with the distribution of wild type NMDA receptor. In addition, florescent protein labelling of NMDA receptor does not interrupt cellular distribution of NMDAR. Moreover, this study shows that N-terminal domain of NR1 subunit is sufficient to prevent degradation of NR2B in the cell. In consideration of this study it can be concluded that EGFP and mCherry labelled NMDA receptors can be used in interaction studies such as FRET and other studies, making use of fluorescent labelling of NMDA receptors, in terms of cellular distribution.

Cornea is the most exterior, avascular and transparent layer of the eye and is about 500 &micro / m in thick. It protects the eye from external objects and it is the main optical element of the eye refracting 70 % of the incoming light. After cataract, corneal diseases and wounds are the second leading cause of the blindness that affects more than 4 million people worldwide. For the highly damaged corneas where the corrections with spectacles or contact lenses cannot be achieved, tissue replacement is the only choice, and is done by cornea transplantation or keratoprostheses. However, due to limited number of donor corneas and the risk of infections during transplantation, and development of glaucoma, necrosis and other complications caused by the keratoprostheses, prevent them from meeting expectations. Tissue engineering is a promising field which emerged from biomaterials science and aims to replace, restore or improve the function of the diseased or injured tissues. In this method, after the production of an ideal scaffold that mimics the natural human tissue, cells of the host are isolated, increased in number, and seeded on the scaffold developed to serve as the microenvironment of the cells. In the current study a 3D corneal stroma replacement was designed to mimic the native stroma. It consisted of 4 films of patterned collagen or collagen blended with Elastin Like Recombinamer (ELR) stacked on top of each other and then crosslinked by dehydrothermal (DHT) treatment. The characterization of the films showed that the pattern fidelity was good and they did not deteriorate after crosslinking. Enzymatic and in situ degradation studies showed that the DHT treatment at 150 oC for 24 h (DHT150) was the optimum condition. The transparency of all the films was quite high where uncrosslinked (UXL) films and DHT150 Col:ELR films yielded the best results. The individual films and 3D construct of 4 stacked films were seeded with isolated human corneal keratocytes (HK) and cultured for 21 days. Cells attached and proliferated well on the single Col and Col:ELR films. However, the proliferation was higher on Col multilayer constructs than their Col:ELR counterparts. Cells were aligned along the patterns of the films while no significant alignment was observed for the cells on unpatterned films. Ultimate tensile strength (UTS) and Young&rsquo / s Modulus (E) of Col and Col:ELR films were significantly lower after a 30 day culture than that of unseeded films of Day 1. Transparency of the seeded Col:ELR films was superior to Col films over a 30 days test and quite close to the transmittance of the native human cornea. It was concluded that the Col and Col:ELR patterned films and their 3D constructs have a significant potential for use as a corneal stroma equivalent.

In the current study, sub-fossil Cladocera collected from the surface sediment of 44 shallow lakes spanning over five latitudes from north to south of Turkey using snap-shot methodology revealed strong impact of salinity on cladoceran community structure. To see the whole picture, sediment cores collected from six of the lakes and long-term monitoring data from two of the lakes were also investigated. Contemporary cladocerans and sub-fossil assemblages were compared to reveal that their responses to salinity changes were highly similar. This lead us to use sub-fossil cladocerans and salinity data from water column together while generating the calibration data set using ordination techniques. Salinity transfer function models were developed utilising weighted averaging techniques. The developed salinity transfer function was applied to cladocera assemblages from dated sediment cores. Hindcasting of the salinity inference model was performed using monitoring data and the reconstructed salinities from two central Anatolian lakes and reflected good linear correlation with the known lake salinity history. This thesis has confirmed that sub-fossil Cladocera is a valuable indicator of historical salinity change and marker for the monitoring of lakes. For the first time, the lake environmental variables and sub-fossil cladoceran species composition from the surface sediments of Turkish shallow lakes were studied and a salinity transfer function was developed to elucidate past salinity change. The approach of the current study has been proven to be reliable while interpreting past salinity conditions. Since monitoring programmes are scarce in Turkey, paleolimnological analyses would be beneficial especially when defining effective restoration strategies.

In the present study Fourier Transform Infrared Spectroscopy was used to examine the effects of streptozotocin-induced diabetes mellitus on the structural components of slow- and fast-twitch rat skeletal muscles, at molecular level. Diabetes mellitus is a chronic disorder of carbohydrate, fat and protein metabolism, which is characterized by hyperglycemia caused by a defective or deficient insulin secretory response. The effect of diabetes is seen on a variety of tissues leading to important secondary complications such as kidney failure, liver dysfunction, cardiac disorders, etc. Skeletal muscle is one of the major tissues determining carbohydrate and lipid metabolism in the body / therefore, is one of the target tissues of diabetes. The two main types of muscle fibers are type I (slow-twitch) and type II (fast-twitch) fibers / having different structural organization and metabolic features. The FTIR spectra revealed a considerable decrease in lipid and protein content of diabetic skeletal muscles, indicating an increased lipolysis and protein breakdown or decreased protein synthesis. Moreover changes in protein structure and conformation were observed. In diabetes, muscle membrane lipids were more ordered and the amount of unsaturated lipids was decreased possibly due to lipid peroxidation. Diabetes caused a decrease in the content of nucleic acids, especially RNA, and hydrogen bonded phospholipids in the membrane structures of skeletal muscles. In all of the spectral parameters investigated slow-twitch muscle was more severely affected from diabetes. Thus, FTIR spectroscopy appears to be a useful method to evaluate the effect of diabetes on skeletal muscle tissues at molecular level.

Breast cancer is the most frequent malignancy among women, especially in Western societies. Highly penetrant genes such as BRCA1 and BRCA2, together with the reproductive history can constitute only 30% of the cause, so there should be other common genes, which may play a role in breast carcinogenesis according to one&#039 / s lifestyle. In our case, the effect of N-acetyl transferases (NAT1, NAT2) and glutathione-S transferases (GSTM1&amp / GSTT1) were investigated, since variations in these genes may alter their enzymatic activity and therefore their capacity to biotransform xenobiotic compounds. To evaluate the potential association between NAT1, NAT2, GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a Turkish study population consisting of 37 histologically confirmed incident breast cancer cases and 34 control subjects with no present or previous history of cancer. The only recognizable difference between case and control groups is the percentage of GSTM1 deletion, 67.6% and 44.1% respectively (p=0.047). The frequency of rapid NAT2 acetylator genotype is 44.4% in cases and 23.5% in controls. Especially, women with NAT2 rapid acetylator and GSTM1 null genotypes were at the elevated risk (OR, 3.8 / CI, 0.9-15.4). NAT1 rapid acetylator genotype showed no association with breast cancer. These results suggest that GSTM1 null genotype is a susceptibility factor for breast cancer, particularly in the presence of NAT2 rapid acetylator genotype.

Some yeast strains secrete extracellular polypeptide toxins known to have potential growth inhibitory activity on sensitive yeast cells. These yeast strains are known as killer yeasts and their toxins are named as killer toxins or killer proteins. Yeast killer proteins are found inhibitory to Gram-positive bacteria in several studies which were based on microbial interactions of the producer strains tested with sensitive strains. K5 type yeast killer protein produced by Pichia anomala NCYC 434 was previously purified and characterized in our laboratory. The protein is glycosilated and has a pI value of 3,7 and molecular mass of 49 kDa, with exo &amp / #946 / -1,3-glucanase activity. Antibacterial activity of the pure K5 type yeast killer protein was tested against 19 clinical isolates of gram-positive bacteria causing skin infections and 2 quality control strains and found to have inhibitory activity on the isolates of Methicillin-sensitive Staphylococcus aureus (MSSA) and Enterococcus faecium. Toxin MIC and MBC ranges were 32 - 256 &micro / g/ml and 64 - &gt / 512 &micro / g/ml respectively. Cell killing analysis revealed that toxin has a bacteriostatic activity and the inhibitory effect starts between 8. and 12. hours. Regrowth of the bacteria is retarded with the increased dose of the toxin. K5 type yeast killer protein might be used as a topical antibacterial agent with its bacteriostatic activity for skin and wound infections caused by MSSA and Enterococcus faecium with appropriate formulation studies upon the antibacterial spectrum determination of the toxin in this study.

Interactions of simvastatin with zwitterionic dipalmitoyl phosphotidylcholine (DPPC) multilamellar liposomes were investigated as a function of temperature and simvastatin concentration. And acyl chain length effect on the simvastatin-model membrane interactions was monitored with DPPC and dimyristoyl phosphotidylcholine (DMPC) lipids. All studies were carried out by two non-invasive techniques, namely Fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). The results showed that as simvastatin concentration increased, the main phase transition temperature decreased, the main phase transition curve broadened, and the characteristic pretransition was disappeared for both DMPC and DPPC model membranes. All concentrations of simvastatin disordered and decreased the fluidity of phospholipid membranes. Analysis of C=O stretching band showed that simvastatin either strengthen the existing hydrogen bonds of the glycerol skeleton closer to the head groups or caused the formation of new hydrogen bonds. A dehydration effect caused by simvastatin around the PO2- functional groups in the polar part of the lipids was monitored. This dehydration effect in the gel phase was more profound than in the liquid crystalline phase for 1, 6, and 12 mol% of simvastatin concentrations. DSC peaks broadened and shifted to lower temperature values by increasing the simvastatin concentration. For both lipids, simvastatin-induced lateral phase separation was observed in the DSC thermograms. Any change caused by the acyl chain length difference of DMPC and DPPC lipids was not observed on the simvastatin-membrane interactions. Also, for both of the lipids similar trends were observed in the FTIR and DSC results. More profound effects of simvastatin on the less stable DMPC membranes were observed.

Zinc (Zn) is an essential micronutrient for the growth and development of all organisms. Zinc deficiency is a widespread micronutrient disorder worldwide, which reduces crop yields and the nutritive value of the grain. Understanding the process of zinc absorption and translocation in crop is essential for this purpose. Zinc is taken up by plants and translocated within plants through high-affinity zinc transporter proteins embedded in the plasma membrane. The Zn transporters are induced under Zn deficiency, and it is speculated that the expression levels of some of zinc transporters are critical for improved tolerance to low zinc. A number of Zn transporters have been cloned from higher plants including rice and Arabidopsis, but little has been done in barley and wheat. This project aims to investigate genes involveld in zinc efficiency mechanism by complementation analysis in yeast, which is double mutant of zinc-transporters, using cDNA expression library from a most zinc efficient barley cultivar, Tokak-157.

Temporal and spatial variations in the Sea of Marmara based on monthly averages of chlorophyll a, which is the major indicator of phytoplankton biomass and primary production, recorded by SeaWiFS and MODIS-Aqua sensors at nearly 100 stations have been analyzed for the period of 1997-2007. Majority of phytoplankton blooms occur during the winter and spring seasons, followed by a smaller secondary bloom during the fall season. The majority of high magnitude blooms occur at the Eastern part of the Sea which may be attributed to an increase in the amount of discharge of water contaminated with nutrients originating on land where the industries are located. The correlations between monthly averages of sea surface temperature (SST) and corresponding chlorophyll a values are statistically significant (inverse) at 1% level, where r= -0.53 and the equation of the fitted model is: Chlorophyll a = 7.09199 &ndash / 0.215402* SST This correlation is expected because a relative decrease in SST is an indicative of upwelling and vertical mixing which are the primary processes for the formation of phytoplankton blooms. We have also found that monthly averages of chlorophyll a recorded by SeaWiFS and MODIS-Aqua are nearly identical and either data set can be used in place of the other.