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Abstract: The hepatotoxicity of drugs is one of the leading causes of drug withdrawal from the pharmaceutical market and high drug attrition rates. Currently, the commonly used hepatocyte models include conventional hepatic cell lines and animal models, which cannot mimic human drug-induced liver injury (DILI) due to poorly defined dose-response relationships and/or lack of human-specific mechanisms of toxicity. In comparison to 2D culture systems from different cell sources such as primary human hepatocytes and hepatomas,, 3D organoids derived from an inducible pluripotent stem cell (iPSC) or adult stem cells are promising accurate models to mimic organ behavior with a higher level of complexity and functionality owing to their ability to self-renewal. Meanwhile, the heterogeneous cell composition of the organoids enables metabolic and functional zonation of hepatic lobule important in drug detoxification and has the ability to mimic idiosyncratic DILI as well. Organoids having higher drug-metabolizing enzyme capacities can culture long-term and be combined with microfluidic-based technologies such as organ-on-chips for a more precise representation of human susceptibility to drug response in a high-throughput manner. However, there are numerous limitations to be considered about this technology, such as enough maturation, differences between protocols and high cost. Herein, we first reviewed the current preclinical DILI assessment tools and looked at the organoid technology with respect to in vitro detoxification capacities. Then we discussed the clinically applicable DILI assessment markers and the importance of liver zonation in the next generation organoid-based DILI models.

Majority of 37 human aminoacyl tRNA synthetases have been incriminated in diverse, mostly recessive, genetic diseases. In accordance with this, we uncovered a novel homozygous valyl-tRNA synthetase 1 (VARS1) gene variant, leading to p.T1068M mutation. As in the previously reported VARS1 mutations, the affected individual harboring p.T1068M was experiencing a neurodevelopmental disorder with intractable seizures, psychomotor retardation, and microcephaly. To link this phenotypic outcome with the observed genotype, we structurally modeled human VARS1 and interpreted p.T1068M within the spatial distribution of previously reported VARS1 variants. As a result, we uncovered that p.T1068M is clustered with three other pathogenic mutations in a 15 amino acid long stretch of the VARS1 anticodon-binding domain. While forming a helix-turn-helix motif within the anticodon-binding domain, this stretch harbors one-fourth of the reported VARS1 mutations. Here, we propose that these clustered mutations can destabilize the interactions between the anticodon-binding and the tRNA synthetase domains and thus hindering the optimal enzymatic activity of VARS1. We expect that the depiction of this mutation cluster will pave the way for the development of drugs, capable of alleviating the functional impact of these mutations.

Yüksek Lisans Tezi, Ortoreksiya nervoza henüz DSM-V yeme bozuklukları kategorisinde yer almayan sağlıklı beslenme takıntısıdır. Sağlık okuryazarlığı ise doğru sağlık kararları alabilmek amacıyla bireylerin sağlıkla alakalı bilgi edinme edinilen bilgileri anlama ve yorumlama kabiliyetidir. Bu tezde Cumhuriyet Üniversitesinde öğrenim gören lisans öğrencilerinde ortoreksiya nervoza eğiliminin belirlenmesi ve sağlık okuryazarlığı ile ilişkisinin incelenmesi amaçlandı. Kesitsel tipte yapılan araştırma 2018-2019 bahar yarıyılında Cumhuriyet Üniversitesinde öğrenim görmekte olan 903 lisans öğrencisi üzerinde üzerinde gerçekleştirildi. Literatür taraması sonucu oluşturulmuş anket formu ile yeme tutum testi, orto-15 ölçeği ve yetişkin sağlık okuryazarlığı ölçeği(YSOÖ) yüz yüze görüşme tekniği ile uygulandı. Veriler SPSS 22.0 programına girilerek analizi yapıldı. Çalışmada ortoreksiya nervoza eğilimi %18,90 (erkeklerde %21,90, kadınlarda %16,40) olarak bulundu. YSOÖ puanları kadınlarda 10,96±2,99, erkeklerde 11,95±2,69 olarak saptandı. Sağlık okuryazarlığı ile öğrenim görülen sınıflar arasında anlamlı ilişki bulundu (p0,05). Sonuç olarak öğrencilerin ortorektik olma durumunun normal olma durumuna göre daha az olduğu tespit edildi. Erkeklerin sağlık okuryazarlığının kadınlara göre daha yüksek olduğu saptandı. Ortoreksiya nervoza eğilimi ve sağlık okuryazarlığı arasında ilişki olmadığı bulundu., Orthorexia nervosa is an obsession with healthy eating that is not yet included in the DSM-V eating disorders category. Health literacy, on the other hand, is the ability of individuals to acquire, understand and interpret information about health in order to make the right health decisions.In this thesis, it was aimed to determine the orthorexia nervosa tendency of undergraduate students studying at Cumhuriyet University and to examine its relationship with health literacy. The cross-sectional study was carried out on 903 undergraduate students studying at Cumhuriyet University in the 2018-2019 Spring Semester.Eating attitude test, ortho-15 scale and adult health literacy scale (YSOÖ) were applied with face-to-face interview technique with a questionnaire form created as a result of literature review. The data were entered into the SPSS 22.0 program and analyzed. In the study, orthorexia nervosa tendency was found to be 18.90% (21.90% in men, 16.40% in women).YSOÖ scores were found as 10.96 ± 2.99 for women and 11.95 ± 2.69 for men. A significant correlation was found between health literacy and the classes studied (p 0.05). As a result, it was determined that the orthorexic condition of the students was less than the normal status. It was found that the health literacy of men was higher than that of women. No relationship was found between orthorexia nervosa tendency and hea lth literacy.

Handedness is the most pronounced behavioral asymmetry in humans. Genome-wide association studies have largely failed to identify genetic loci associated with phenotypic variance in handedness, supporting the idea that the trait is determined by a multitude of small, possibly interacting genetic and non-genetic influences. However, these studies typically are not capable of detecting influences of rare mutations on handedness. Here, we used whole exome sequencing in a Turkish family with history of consanguinity and overrepresentation of left-handedness and performed quantitative trait analysis with handedness lateralization quotient as a phenotype. While rare variants on different loci showed significant association with the phenotype, none was functionally relevant for handedness. This finding was further confirmed by gene ontology group analysis. Taken together, our results add further evidence to the suggestion that there is no major gene or mutation that causes left-handedness.

Handedness is the most pronounced behavioral asymmetry in humans. Genome-wide association studies have largely failed to identify genetic loci associated with phenotypic variance in handedness, supporting the idea that the trait is determined by a multitude of small, possibly interacting genetic and non-genetic influences. However, these studies typically are not capable of detecting influences of rare mutations on handedness. Here, we used whole exome sequencing in a Turkish family with history of consanguinity and overrepresentation of left-handedness and performed quantitative trait analysis with handedness lateralization quotient as a phenotype. While rare variants on different loci showed significant association with the phenotype, none was functionally relevant for handedness. This finding was further confirmed by gene ontology group analysis. Taken together, our results add further evidence to the suggestion that there is no major gene or mutation that causes left-handedness.

Heparin is a linear, undranched, highly-sufated glycosaminoglycan, primarily axists helical structure. In addition to its role as an anticoagulant, Heparin interacts with proteins to modulate their activities.

To evaluate the 1-year follow-up results of cultivated limbal epithelial cell (CLEC) transplantation in unilateral limbal stem cell deficiency (LSCD).One-year follow-up results of five unilateral LSCD patients who had undergone CLEC transplantation were evaluated. Parameters for this evaluation were: fluorescein staining of ocular surface, corneal vascularization and status of epithelium with slit lamp, and visual acuity. 1.5-mm limbal biopsy was performed from the superior limbus of the healthy eyes, broke into two equal pieces, expanded on human amniotic membrane (hAM) and inserts for 14 days until getting 20 mm in size. CLECs on hAMs were used directly, and cells on inserts were used after detachment procedure. The symblepharon and pannus tissues were removed, superficial keratectomy was performed. CLEC on hAMs were transplanted with the epithelial side up onto the bare corneal stroma, sutured to the conjunctiva with 10-0 nylon sutures. Free CLEC layer from insert was placed on hAM as a second layer, additional hAM was used as a protective layer all over other tissues.Median age was 44.4 years (14-71). The etiology was chemical burn in all patients. Median duration of symptoms was 10 years (2-18), median follow-up period was 12.6 (12-12.5) months. Preoperative best corrected visual acuities (BCVA) were light perception in three patients, counting fingers at 50 cm in one patient and 3/10 in one patient. Visions were improved in all patients. Postoperative BCVA 12 months after the surgery were between counting fingers at 3 meters to 6/10. There was a temporary hemorrhage between the two layers of hAMs in one patient at the early postoperative period. Peripheral corneal vascularization has occurred in three patients, in patient corneal vascularization has reached to the paracentral area.CLEC transplantation is an efficient treatment option for unilateral LSCD in mid-long term.

Kestanelerde, hasat öncesi, hasat ve hasat sonrası dönemlerde meyve kalite özellikleri değişiminin ortaya konması ve karşılaştırılması amacıyla yürütülmüştür. Çalışmada kestaneler n normal (geleneksel)ve soğuk depo koşullarında (soğuk hava deposunda) muhafaza edilmiştir. 2010 yılı ürün yılında; hasat öncesi, hasat ve hasat sonrası Ekim ayı başı-Aralık ayı sonu arasındaki muhafaza süresince iki hafta aralıklarla alınan, meyve örneklerinde fiziksel ve biyokimyasal analizler yapılmıştır. Bu amaçla; meyve boyutları (en, boy, yükseklik, meyve indeksi), meyve kabuğu ve eti rengi *, su aktivitesi (aw) ve toplam şeker, nişasta ve karbonhidrat miktarı, *; tanen miktarı, aflatoksin B1, B2, G1, G2, toplam aflatoksin (ppb) miktarları belirlenmiştir.Geleneksel ve soğuk hava deposunda muhafaza ile kestanelerde depolama süresi arttıkça toplam şeker miktarının (%) arttığı, bununla birlikte toplam nişasta miktarının (%) ise azaldığı saptanmıştır. Muhafaza süresi uzamasıyla birlikte kestanelerde muhafaza şekline bağlı olarak aflatoksin bulaşıklığının görülebileceği sonucuna varılmıştır.Anahtar sözcükler: Kestane, hasat, depolama, kalite, biyokimyasal Traditional storage and cold storage room have been used in this trial, which was performed in order to exhibit and compare the changes in fruit quality properties of chestnuts during the pre-harvest, harvest and post-harvest terms. In this trial, which has been set up on Year 2010 harvest season, during pre-harvest, harvest and post-harvest storages, physical and biochemical analyses have been performed with fruit samples taken approximately once in every two weeks, between the beginning of September and the end of December. For that purpose, fruit sizes (width, length, height, fruit index), peel and pulp colors (L*, a*, b*, hue, chroma), water activity (aw) and amounts of total sugar, starch and carbohydrates (%). amount of tannin (%), amounts of aflatoxin B1, B2, G1, G2, total aflatoxins (ppb) have been detected. With storage in traditional and cold storage rooms, it has been observed that total amount of sugar (%) in chestnuts has increased whereas total amount of starch (%) has declined. In addition to this, aflotoxin contamination could be observed in chestnuts in the event of elongation of storage period depending on the type of storage. 87