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    Characterization of Cryphonectria parasitica From Native Chestnut Trees in Kaz Mountain (Mount Ida)
    (2018) Özkılınç, Hilal; Kozma, Zerrin; Pekdemir, Burcu; Gülnar, Birgul
    Cryphonectria parasitica is a causal agent of chestnut blight worldwide and it dramatically affectsnatural chestnut trees in Kaz Mountain (Mount Ida). Different biological control approaches have been proposed toconstrain the disease. The pathogen has mating system with two alternate idiomorphs which may increasepathogen genetic variability due the recombination events. In this study, C. parasitica isolates were diagnosed withpartial sequencing of Translation Elongation Factor-1? (Ef-1?) gene, tested for their pathogenicity, evaluated fortheir mating types, and the isolates of Trichoderma sp. which were isolated from the same lesion where someisolates of C. parasitica were obtained were investigated for antagonistic effect on C. parasitica. It was notdetected any mutation in sequenced part of Ef-1? gene. All the isolates were confirmed as pathogen in in vitroassays by inoculation to apple fruit. Only one mating type (Mat1-1) was detected for some of the isolates.Trichoderma sp. isolates were suppressed in vitro growth rate of C. parasitica. Both C. parasitica andTrichoderma sp. caused necrotic symptoms on the fruits once they were inoculated on apple, but, Trichoderma sp.did not affect lesion development caused by C. parasitica. Overall results present that wild chestnut trees in KazMountain are under threat of chestnut blight pathogens having similar aggressiveness and genetic identity and,isolates of Trichoderma sp. obtained in this study should be assessed by in vivo experiments for their biocontrolability against to C. parasitica.
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    Exploring the diverse biological significance and roles of fucosylated oligosaccharides
    (Frontiers Media Sa, 2024) Pekdemir, Burcu; Karav, Sercan
    Long since, carbohydrates were thought to be used just as an energy source and structural material. However, in recent years, with the emergence of the field of glycobiology and advances in glycomics, much has been learned about the biological role of oligosaccharides, a carbohydrate polymer containing a small number of monosaccharides, in cell-cell interaction, signal transduction, immune response, pathogen adhesion processes, early embryogenesis, and apoptosis. The function of oligosaccharides in these processes is diversified by fucosylation, also known as modification of oligosaccharides. Fucosylation has allowed the identification of more than 100 different oligosaccharide structures that provide functional diversity. ABO blood group and Lewis antigens are among the best known fucosyl-linked oligosaccharides. In addition, the antigens in the ABO system are composed of various sugar molecules, including fucosylated oligosaccharides, and Lewis antigens are structurally similar to ABO antigens but differ in the linkage of sugars. Variation in blood group antigen expression affects the host's susceptibility to many infections. However, altered expression of ABO and Lewis antigens is related with prognosis in carcinoma types. In addition, many pathogens recognize and bind to human tissues using a protein receptor with high affinity for the fucose molecule in glycoconjugates, such as lectin. Fucosylated oligosaccharides also play vital roles during fertilization and early embryogenesis. Learning and memory-related processes such as neurite growth, neurite migration, and synapse formation seen during the development of the brain, which is among the first organs to develop in embryogenesis, are regulated by fucosylated oligosaccharides. In conclusion, this review mentions the vital roles of fucosylated oligosaccharides in biology, drawing attention to their importance in the development of chemical tools to be used in function analysis and the investigation of various therapeutic targets.
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    Fucosidosis: A Review of a Rare Disease
    (Mdpi, 2025) Pekdemir, Burcu; Bechelany, Mikhael; Karav, Sercan
    Fucosidosis is a rare lysosomal storage disease caused by alpha-L-fucosidase deficiency following a mutation in the FUCA1 gene. This enzyme is responsible for breaking down fucose-containing glycoproteins, glycolipids, and oligosaccharides within the lysosome. Mutations in FUCA1 result in either reduced enzyme activity or complete loss of function, leading to the accumulation of fucose-rich substrates in lysosomes. Lysosomes become engorged with undigested substrates, which leads to secondary storage defects affecting other metabolic pathways. The central nervous system is particularly vulnerable, with lysosomal dysfunction causing microglial activation, inflammation, and neuronal loss, leading to the neurodegenerative symptoms of fucosidosis. Neuroinflammation contributes to secondary damage, including neuronal apoptosis, axonal degeneration, and synaptic dysfunction, exacerbating the disease process. Chronic neuroinflammation impairs synaptic plasticity and neuronal survival, leading to progressive intellectual disability, learning difficulties, and loss of previously acquired skills. Inflammatory cytokines and lysosomal burden in motor neurons and associated pathways contribute to ataxia, spasticity, and hypotonia, which are common motor symptoms in fucosidosis. Elevated neuroinflammatory markers can increase neuronal excitability, leading to the frequent occurrence of epilepsy in affected individuals. So, fucosidosis is characterized by rapid mental and motor loss, along with growth retardation, coarse facial features, hepatosplenomegaly, telangiectasis or angiokeratomas, epilepsy, inguinal hernia, and dysostosis multiplex. Patients usually die at an early age. Treatment of fucosidosis is a great challenge, and there is currently no definitive effective treatment. Hematopoietic cell transplantation studies are ongoing in the treatment of fucosidosis. However, early diagnosis of this disease and treatment can be effective. In addition, the body's immune system decreases due to chemotherapy applied after transplantation, leaving the body vulnerable to microbes and infections, and the risk of death is high with this treatment. In another treatment method, gene therapy, the use of retroviral vectors, is promising due to their easy integration, high cell efficiency, and safety. In another treatment approach, enzyme replacement therapy, preclinical studies are ongoing for fucosidosis, but the blood-brain barrier is a major obstacle in lysosomal storage diseases affecting the central nervous system. Early diagnosis is important in fucosidosis, a rare disease, due to the delay in the diagnosis of patients identified so far and the rapid progression of the disease. In addition, enzyme replacement therapy, which carries fewer risks, is promising.
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    Functional chocolate: exploring advances in production and health benefits
    (Wiley, 2024) Saritas, Suemeyye; Duman, Hatice; Pekdemir, Burcu; Rocha, Joao Miguel; Oz, Fatih; Karav, Sercan
    Chocolate has been a part of human consumption for millennia, serving as a confection, medicine and aphrodisiac. Chocolate consumption is increasing worldwide, and independent of the age or social background. The substantial content of chocolate may provide consumers with antioxidant, anti-inflammatory, antimicrobial, antiallergenic, and anticarcinogenic benefits. Beyond such properties, diverse bioactive ingredients are utilised in the creation of functional chocolate products aiming at promoting health and meeting the modern consumers' demands and market orientations. These products are primarily focused on enhancing nutraceutical effects, such as antioxidant activity, protein content and prebiotic effects. Additionally, the use of A2 milk powder in chocolate production holds promising expectations towards enhancing the digestibility of the products. Due to the superior affinity of proteolytic enzymes, A2 milk can be digested more easily than A1 milk. In this way, with the addition of A2 milk to chocolate, it may become more easily digestible. The objectives of this review are a comprehensive understanding of the evolution of chocolate consumption, its health benefits, and the contemporary innovations in chocolate production. Additionally, the potential for developing easily digestible, functional chocolates made from A2 milk, which could rejuvenate functional chocolate production, is discussed in this article. The bioactive components contained in various types of chocolate have been shown in the graphical abstract. The bioactive components and amounts contained vary according to the type of chocolate. image
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    Immobilization of a Bifidobacterial Endo-ss-N-Acetylglucosaminidase to Generate Bioactive Compounds for Food Industry
    (Frontiers Media Sa, 2022) Pekdemir, Burcu; Duman, Hatice; Arslan, Aysenur; Kaplan, Merve; Karyelioglu, Melda; ozer, Tolgahan; Kayili, Haci Mehmet
    Conjugated N-glycans are considered next-generation bioactive prebiotic compounds due to their selective stimulation of beneficial microbes. These compounds are glycosidically attached to proteins through N-acetylglucosamines via specific asparagine residue (AsN-X-Ser/Thr). Certain bacteria such as Bifidobacterium longum subspecies infantis (B. infantis) have been shown to be capable of utilizing conjugated N-glycans, owing to their specialized genomic abilities. B. infantis possess a unique enzyme, Endo-ss-N-acetylglucosaminidase (EndoBI-1), which cleaves all types of conjugated N-glycans from glycoproteins. In this study, recombinantly cloned EndoBI-1 enzyme activity was investigated using various immobilization methods: 1) adsorption, 2) entrapment-based alginate immobilization, 3) SulfoLink-, and 4) AminoLink-based covalent bonding immobilization techniques were compared to develop the optimum application of EndoBI-1 to food processes. The yield of enzyme immobilization and the activity of each immobilized enzyme by different approaches were investigated. The N-glycans released from lactoperoxidase (LPO) using different immobilized enzyme forms were characterized using MALDI-TOF mass spectrometry (MS). As expected, regardless of the techniques, the enzyme activity decreased after the immobilization methods. The enzyme activity of adsorption and entrapment-based alginate immobilization was found to be 71.55% +/- 0.6 and 20.32% +/- 3.18, respectively, whereas the activity of AminoLink- and SulfoLink-based covalent bonding immobilization was found to be 58.05 +/- 1.98 and 47.49% +/- 0.30 compared to the free form of the enzyme, respectively. However, extended incubation time recovery achieved activity similar to that of the free form. More importantly, each immobilization method resulted in the same glycan profile containing 11 different N-glycan structures from a model glycoprotein LPO based on MALDI-TOF MS analysis. The glycan data analysis suggests that immobilization of EndoBI-1 is not affecting the enzyme specificity, which enables full glycan release without a limitation. Hence, different immobilization methods investigated in this study can be chosen for effective enzyme immobilization to obtain bioactive glycans. These findings highlight that further optimization of these methods can be a promising approach for future processing scale-up and commercialization of EndoBI-1 and similar enzymes.
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    Lactoferrin: neuroprotection against Parkinson's disease and secondary molecule for potential treatment
    (Frontiers Media Sa, 2023) Eker, Furkan; Bolat, Ecem; Pekdemir, Burcu; Duman, Hatice; Karav, Sercan
    Parkinson's disease (PD) is the second-most common neurodegenerative disease and is largely caused by the death of dopaminergic (DA) cells. Dopamine loss occurs in the substantia nigra pars compacta and leads to dysfunctions in motor functions. Death of DA cells can occur with oxidative stress and dysfunction of glial cells caused by Parkinson-related gene mutations. Lactoferrin (Lf) is a multifunctional glycoprotein that is usually known for its presence in milk, but recent research shows that Lf is also found in the brain regions. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known mitochondrial toxin that disturbs the mitochondrial electron transport chain (ETC) system and increases the rate of reactive oxygen species. Lf's high affinity for metals decreases the required iron for the Fenton reaction, reduces the oxidative damage to DA cells caused by MPTP, and increases their surveillance rate. Several studies also investigated Lf's effect on neurons that are treated with MPTP. The results pointed out that Lf's protective effect can also be observed without the presence of oxidative stress; thus, several potential mechanisms are currently being researched, starting with a potential HSPG-Lf interaction in the cellular membrane of DA cells. The presence of Lf activity in the brain region also showed that lactoferrin initiates receptor-mediated transcytosis in the blood-brain barrier (BBB) with the existence of lactoferrin receptors in the endothelial cells. The existence of Lf receptors both in endothelial cells and DA cells created the idea of using Lf as a secondary molecule in the transport of therapeutic agents across the BBB, especially in nanoparticle development.
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    Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health
    (Mdpi, 2024) Pekdemir, Burcu; Raposo, Antonio; Saraiva, Ariana; Lima, Maria Joao; Alsharari, Zayed D.; Binmowyna, Mona N.; Karav, Sercan
    The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood-brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain's immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.
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    Recombinant production of a glycosidase by using an in-vivo cloning system and its immobilization via different strategies
    (Çanakkale Onsekiz Mart Üniversitesi, 2020) Pekdemir, Burcu; Karav, Sercan
    İnsan sütü su hariç %54 laktoz, %32 yağ, %8 serbest oligosakkaritler (serbest glikanlar) ve %6 protein içermektedir. Serbest glikanlar insan sütünde yüksek miktarda bulunmasına rağmen, bu glikanların bebekler tarafından sindirilmesi mümkün değildir. Bir araştırmada, bu bileşiklerin aslında faydalı bakterilerin gelişiminde ve dolayısıyla bebeklerin bağışıklık sistemini güçlendirmede kullanıldığı gösterilmiştir (Lo Cascio ve diğerleri, 2007). Serbest glikanların çok değerli bir prebiyotik kaynağı olduğunun anlaşılmasından sonra, bu bileşiklere olan ilgi hızla artmıştır ve önemli bir araştırma konusu haline gelmiştir. Anne sütünün endüstriyel anlamda üretilme olanağının çok sınırlı olması ve serbest glikanların diğer sütlerdeki oranının (inek sütü % 0.1) oldukça düşük olması nedeniyle, anne sütüne erişim olanağı olmayan bebeklere, serbest glikanların temini konusunda çok ciddi bir açık bulunmaktadır. Bu eksikliği gidermek amacı ile araştırmacılar kimyasal yapıca glikan özelliği gösterebilecek başka bileşiklerin keşfine yönelmiştir ve serbest glikanlara oldukça benzer başka bileşiklerin proteinlere N- ve O-glikosidik bağlarla bağlı şekilde (glikoproteinler) bulunduğunu göstermişlerdir. Glikanlar, prebiyotik etkileri yanında, hücreler arası etkileşimde, proteinlerin düzgün bir şekilde katlanmasında ve stabilizasyonunda da önemlidir. Fakat glikanların bu biyolojik ve fiziko-kimyasal özellikleri, glikoproteinlerden ayrılmaları için kullanılan yöntemlerin yetersizliği yüzünden tam olarak anlaşılamamıştır. Günümüzde kullanılan kimyasal ve enzimatik yöntemler, bütün glikanları glikoproteinlerden ayıramamakta ya da bu yöntemler güçlü kimyasal ve ısı kullanımı gerektirdiğinden, glikanların ve geride kalan protein kısmının yapısını bozmaktadır. Bu eksikliği gidermek için yeni bir enzim olan endo-?-N- asetilglukozaminidaz, Bifidobacterium longum subsp. infantis ATCC 15697'dan ilk 2015 yılında izole edilmistir (Karav ve diğerleri, 2015a). Bu enzim herhangi bir ısıl işleme ve kimyasal kullanımına gereksinim duymadan, glikanların biyolojik etkinliği kaybolmadan izole edilmesine olanak sağlamaktadır. Bu yüzden günümüzde glikanların yüksek ölçüde izole edilip biyolojik görevlerinin araştırılmasına olanak sağlayan tek strateji olarak bu enzimin kullanımı kabul edilmektedir. Bu tez çalışmasında ilk olarak, ticari olarak temini mümkün olmayan endo-?-N-asetilglukozaminidaz enziminin rekombinant olarak üretilmesi hedeflenmiştir. Bu enzimi kodlayan genin moleküler klonlaması için yeni bir teknik olan in-vivo klonlama tekniği kullanılmıştır ve farklı immobilizasyon stratejileri (adsorpsiyon, hapsedilme ve kovalent bağlama) denenerek enzimin geri kazanımının sağlanması hedeflenmiştir. Elde edilen immobilize enzimlerin aktiviteleri model terapötik proteinler üzerinde denenmiş ve serbest enzimden sonra en yüksek aktivite gösteren enzim formunun adsorbsiyon stratejisi ile immobilize edilen enzim olduğu görülmüştür. Daha sonra elde edilen glikanlar ileri kütle spektrometresi kullanılarak karakterize edilmiştir. Uzun süreli inkübasyon sonucunda, farklı stratejiler ile immobilize edilen enzimlerin bütün N-bağlı glikanları kesebildiği gösterilmiştir.
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    Role of milk glycome in prevention, treatment, and recovery of COVID-19
    (Frontiers Media Sa, 2022) Kaplan, Merve; Sahutoglu, Arif Sercan; Saritas, Sumeyye; Duman, Hatice; Arslan, Aysenur; Pekdemir, Burcu; Karav, Sercan
    Milk contains all essential macro and micro-nutrients for the development of the newborn. Its high therapeutic and antimicrobial content provides an important function for the prevention, treatment, and recovery of certain diseases throughout life. The bioactive components found in milk are mostly decorated with glycans, which provide proper formation and modulate the biological functions of glycosylated compounds. The glycome of milk consists of free glycans, glycolipids, and N- and O- glycosylated proteins. Recent studies have shown that both free glycans and glycan-containing molecules have antiviral characteristics based on different mechanisms such as signaling, microbiome modulation, natural decoy strategy, and immunomodulatory action. In this review, we discuss the recent clinical studies and potential mechanisms of free and conjugated glycans' role in the prevention, treatment, and recovery of COVID-19.