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Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100-fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub-nanomolar IC50, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)-MoonTag provides protection against SARS-CoV-2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS-CoV-2 infections., Koç University Isbank Center for Infectious Diseases (KUISCID); Koç University Research Center for Transla-tional Medicine (KUTTAM)

Soluble ACE2 (sACE2) decoy receptors are promising agents to inhibit SARS-CoV-2, as their efficiency is less likely to be affected by common escape mutations in viral proteins. However, their success may be limited by their relatively poor potency. To address this challenge, we developed a large decoy library of sACE2 fusion proteins, generated with several protease inhibitors or multimerization tags. Among these decoys, multimeric sACE2 consisting of SunTag or MoonTag systems, which were originally utilized for signal amplification or gene activation systems, were extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates. These novel sACE2 fusion proteins exhibited greater than 100-fold SARS-CoV-2 neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag in combination with a more potent version of sACE2, which has multiple point mutations for greater binding (v1), achieved near complete neutralization at a sub-nanomolar range, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutant versions of Spike, alpha, beta, gamma or delta variants, were also neutralized efficiently with SunTag or MoonTag fused sACE2(v1). Finally, therapeutic treatment of sACE2(v1)-MoonTag provided protection against SARS-CoV-2 infection in an in vivo mouse model. Overall, we suggest that the superior activity of the sACE2-SunTag or sACE2-MoonTag fusions is due to the greater occupancy of the multimeric sACE2 receptors on Spike protein as compared to monomeric sACE2. Therefore, these highly potent multimeric sACE2 decoy receptors may offer a promising treatment approach against SARS-CoV-2 infections.One Sentence SummaryMultimerization of sACE2 markedly enhanced the neutralization of SARS-CoV-2 by blocking multiple viral spike proteins simultaneously.

Oligodonti, çeşitli nedenlerle altı ya da daha fazla dişin oluşmamasına bağlı izlenen bir sayı anomalisidir. Görülme sıklığı kıtalara, toplumlara ve cinsiyetlere göre farklılık göstermektedir. Diş gelişimi ağırlıklı olarak genetik kontrolü altında ilerlemektedir. Diş gelişimi sırasında 200'den fazla gen rol oynamakta ve bu genlerde meydana gelen mutasyonların, oligodontiye neden olduğu düşünülmektedir. Oligodontiye neden olan genlerde, bireyler arası önemli varyasyonlar bulunmakta ve oluşan gen mutasyonlarının oligodontiyle birlikte bazı anomalilere ve kanserlere neden olduğu ifade edilmektedir. Oligodontili bireylerde etiyolojinin belirlenmesi, bu durumu etkileyen genlerin, ileride neden olabileceği çeşitli sağlık problemlerinin de önüne geçilmesi açısından önem taşımaktadır. Derlememiz, daha önceki yayınlarda bildirilmiş olan oligodonti ile ilişkili insan genomundaki mutasyonları gözden geçirmek ve dahil olan farklı genler hakkında gene özgü detaylar sağlamak için hazırlanmıştır.Anahtar Kelimeler: Diş Eksikliği, Etiyoloji, Genetik GENETIC BASIS OF OLIGODONTIAAbstractOligodontia is a number anomaly that is observed due to the absence of six or more teeth for various reason. The prevalance of oligodontia have varies according to continents, societies and genders. Tooth development have proceed predominantly genetic control. More than 200 genes have play a role during dental development, and mutations in these genes are thought to cause oligodontia.There are important inter-individual differences in the genes that cause oligodontia, and it is stated that the gene mutations that cause oligodontia cause some anomalies and cancers. The determination of the etiology in individuals with oligodontia is important in order to prevent the various health problems that may be caused by the genes that affect this condition.Our review was prepared to review mutations in the human genome associated with oligodontia reported in previous publications and to provide gene-specific details about the different genes involved.Keywords: Tooth Agenesis, Etiology, Genetics

Objective: This study aimed to determine the prevalence and distribution of non-syndrome-related oligodontia in Turkish-children in Isparta and its surroundings.Materials and Method: The records of patients who were admitted to the Department of Pedodontics, Faculty of Dentistry of Süleyman Demirel University between 1999-2018, and diagnosed with oligodontia were searched. One-hundred-twelve individuals between the ages of 6 and 18 who did not have any systemic disorders, and missing ≥6 teeth except the third molars were included in the study. The distribution of detected tooth agenesis according to missing teeth, gender, and jaws and tooth agenesis patterns were examined. The frequency of tooth agenesis was given in numbers-percentages, and the Mann-Whitney U test was applied to the distribution of gender and missing teeth. The frequency analysis was calculated using Tooth Agenesis Code (TAC) values to determine tooth agenesis patterns.Results: The incidence of non-syndrome-related oligodontia in Turkish-children in Isparta and its surroundings was found to be 0.08%. The number of missing teeth per individual was found to be 9.05 and the most commonly missing teeth were observed as lower/upper second premolars. When the tooth agenesis was compared between genders and jaws, the differences were not statistically significant. Commonly observed tooth agenesis patterns were a combination of premolars and lateral incisor.Conclusion: According to the results, in Isparta and its surroundings, the presence of oligodontia was detected in 8 out of 10,000 children. Along with the early diagnosis, alternative treatment can be applied considering the severity and distribution of oligodontia., Amaç: Bu çalışmanın amacı, Isparta ve çevresinde yaşayan Türk çocuklarında oligodontinin prevalansı ve dağılımını belirlemektir.Gereç ve Yöntem: Süleyman Demirel Üniversitesi Diş Hekimliği Fakültesi, Pedodonti Anabilim Dalına 1999-2018 yılları arasında başvuran ve oligodonti tanısı konulmuş hasta kayıtları tarandı. Herhangi bir sistemik rahatsızlığı olmayan, üçüncü büyük azı dişleri hariç 6 ve daha fazla dişi eksik olan 6-18 yaş aralığında 112 birey çalışmaya dahil edildi. Saptanan diş eksikliklerinin, eksik diş sayılarına, dişlere, cinsiyete ve çenelere göre dağılımı ve diş eksikliği paternleri incelendi. Diş eksikliği görülme sıklığı sayı ve yüzde olarak tablolanıp, cinsiyet ve eksik dişlerin çenelere göre dağılımında Mann-Whitney U testi uygulandı. Diş eksikliği paternlerini belirlemek için Tooth Agenesis Code/Diş Eksikliği Kodu (TAC) değerleri verilerine frekans analizi yapıldı.Bulgular: Çalışmamızda Isparta ve çevresinde yaşayan Türk çocuklarında, sendroma bağlı olmayan oligodontinin görülme sıklığı %0.08 oranında saptandı. Birey başına düşen konjenital eksik diş sayısı 9.05 olarak bulundu ve eksikliği en sık görülen dişler, alt ve üst 2. küçük azı dişleri olarak gözlendi. Diş eksikliği cinsiyetler ve çeneler arasında karşılaştırıldığında aradaki farklar istatistiksel olarak anlamlı bulunmadı. Yaygın izlenen eksik diş paternleri, üst çenede küçük azı ve lateral kesici kombinasyonu iken, alt çenede küçük azı dişleri ve lateral kesici dişlerin kombinasyonu şeklinde oldu.Sonuç: Elde edilen sonuçlar dahilinde, Isparta ve çevresinde her on bin çocuktan 8’inde oligodonti varlığı tespit edildi. Oligodontinin erken teşhisi ile birlikte, şiddeti ve dağılımı göz önüne alınarak uygulanabilecek alternatif tedaviler önemli olabilir.

Amelogenesis imperfecta (AI) is one of the developmental enamel defects. In patients with AI, as well as enamel defects, some dental anomalies are encountered and may affect tooth development. For children whose enamel structure is not normal, whether an accurate result can be obtained by dental age determination methods is not clear. The aims of this study are to determine the dental age for the assessment of tooth development in patients with AI by 3 different methods, to decide a method that will present the most accurate result to the chronological age, and to build a basis in terms of postmortem identification. The records of patients who were referred to the Department of Pediatric Dentistry between the years of 1999 and 2018, and diagnosed with AI were reviewed. At the age of 6-15 years, 58 patients (33 males-25 females) (Group I) with AI were determined. A total of 116 healthy individuals (66 males-50 females) (Group II) who were age and gender matched with the AI group were selected as the control group. Chronological age was calculated, and Nolla's, Demirjian's and Haavikko's methods were used to estimate dental age. Chronological and dental ages were compared according to the group and gender. The accuracy of three methods was also evaluated. There was no statistical significant differences for the tooth development in terms of group and gender. Dental age was over-estimated by Demirjian's method and under-estimated by Nolla's and Haavikko's methods. Haavikko's and Nolla's methods were more accurate in the dental age estimation. AI did not present an impact on the dental development. By using particularly Haavikko's method, the possible margin of error in evaluations of dental development can be reduced. Similar studies comprising other defects affecting the tooth structure and morphology are also necessary.

Serebral palsi (SP), fetal ya da yeni doğanda, gelişimini sürdürmekte olan beyin dokularında meydana gelen, ilerleyici olmayan, postür bozukluğuna yol açan, hareketi kısıtlayan, kalıcı bir grup hastalıktır. SP'ye özgü nöromüsküler problemler, farklı yollarla ağız sağlığını etkilemektedir. Diş hekiminin SP’li bireylerle ilgili sıklıkla karşılaşabileceği oral problemler arasında; bruksizm, dental erozyon, maloklüzyon, travmatik diş yaralanmaları, periodontal hastalık, diş çürükleri ve mine defektleri bulunmaktadır. Bu derlemede, SP’li çocuklarda yaygın görülen oral problemler, ağız dışına salya akışı ve tedavi önerileri ile birlikte diş hekimlerinin yaklaşımı, hasta ve ebeveyn/bakıcılarına tavsiyeleri hakkında bilgi verilmektedir.