The apoptotic protease activating factor 1 (APAF1) gene encodes a cytoplasmic protein that initiates apoptosis and is a crucial factor in the mitochondria-dependent death pathway. APAF1 is implicated in many pathways such as apoptosis, neurodegenerative diseases, and cancer. The purpose of this study was to predict deleterious/damaging SNPs in the APAF1 gene viain silicoanalysis. To this end, APAF1 missense SNPs were obtained from the NCBI dbSNP database. In silico analysis of the missense SNPs was carried out by using publicly available online software tools. The stabilization and three-dimensional modeling of mutant proteins were also determined by using the I-Mutant 2.0 and Project HOPE webservers, respectively. In total, 772 missense SNPs were found in the APAF1 gene from the NCBI dbSNP database, 18 SNPs of which were demonstrated to be deleterious or damaging. Of those, 13 SNPs had a decreasing effect on protein stability, while the other 5 SNPs had an increasing effect. Based on the modeling results, some dissimilarities of mutant type amino acids from wild-type amino acids such as size, charge, and hydrophobicity were revealed. The SNPs predicted to be deleterious in this study might be used in the selection of target SNPs for genotyping in disease association studies. Therefore, we could suggest that the present study could pave the way for future experimental studies.

Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of concern that have been reported worldwide, the new manifestations of neurological manifestations, the current therapeutic drug targets for its treatment, vaccine candidates and their efficacy, implantation of convalescent plasma, and neutralization of mAbs. We review specific clinical questions, including many emerging neurological effects and respiratory tract injuries, as well as new potential biomarkers, new studies in addition to known therapeutics, and chronic diseases of vaccines that have received immediate approval. To answer these questions, further understanding of the burden kinetics of COVID-19 and its correlation with neurological clinical outcomes, endogenous antibody responses to vaccines, pharmacokinetics of neutralizing mAbs, and action against emerging viral mutant variants is needed.

Alzheimer hastalığı (AH), β-amiloid (Aβ) senil plakların ve nörofibriler yumakların patolojik birikimi ile karakterize olan ilerleyici bir nörodejeneratif hastalıktır. γ-sekretaz, AH nedeni olan amiloid β peptidi (Aβ) üretmektedir. γ-sekretaz makromoleküler bir komplekstir ve APH1A geninin kodladığı protein bu komplekste yer almaktadır. Bu çalışmada, APH1A genindeki yanlış anlamlı (missense) tek nükleotid polimorfizmlerinin (SNP) proteinin yapısı ve stabilizasyonu üzerindeki olası zararlı etkilerinin in silico yöntemler kullanılarak belirlenmesi amaçlanmıştır. Zararlı SNP'lerin tahmin edilmesi için PolyPhen-2 ve SIFT yazılım araçları, protein stabilizasyonu değişimlerinin tespit edilmesi için I-Mutant 2.0 yazılımı, yabanıl ve mutant tip proteinlerin üç boyutlu modellemeleri için Project HOPE yazılım aracı kullanılmıştır. Sonuçlar, APH1A geninde yer alan toplam 3567 SNP'nin 257 tanesinin yanlış anlamlı SNP olduğunu göstermiştir. 257 SNP'nin in silico analizlerine göre, rs11548266, rs74126634, rs145324799, rs199961673, rs370361277, rs370719475 ve rs376071112 polimorfizmlerinin zararlı etkilerinin olabileceği belirlenmiştir. Çalışmamızda gerçekleştirdiğimiz in silico analizler, Alzheimer hastalığı ile ilgili APH1A geninde yer alan 3567 SNP'nin tamamının genotiplenmesi yerine proteinin yapısı ve stabilizasyonuna zararlı etkisi olabilecek SNP'lerin genotiplenmesine ilişkin veri sağlamaktadır. Dolayısıyla, zararlı olduğu tespit edilen SNP'ler genotipleme çalışmalarının en önemli basamağı olan SNP seçiminde ve deney tasarımında kullanılabilecektir. Bu nedenle, elde ettiğimiz sonuçların Alzheimer hastalığı ile ilgili gelecekte yapılacak olan hem deneysel hem de in silico çalışmalara katkı sağlayacağı düşünülmektedir.

No abstract

Background. The determination of the genetic endowment of athletic performance in sports is an important step in developing personal training sessions or nutritional supplements for success in sports. Information about the genetic parameters responsible for these metabolisms will help sport's scientist to develop new insights for better performance. Muscle metabolism is one of the key points in better personal athletic performance. Objectives. The aim of this study is to analyze the distribution of the methylenetetrahydrofolate reductase enzyme (MTHFR) rs1801133 (C677T) genotype and allele distribution in a Turkish professional cyclist cohort. Methods. There were 25 Turkish cyclists enrolled in the study. Peripheral blood used for DNA isolation and the conventional polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) methodology were used for genotyping. Results. There were 14 (56%), 10 (40%) and 1 (4%) cyclist who had CC, CT, and TT genotypes, respectively. C allele was counted as 38 (76%), and T alleles as 12 (24%). 9 (50%) of the male cyclist had CC, 8 (44.4%) had CT and only 1 had TT (5.6%) genotypes. C allele was counted as 26 (72.2%), and the T allele as 10 (27.8%) in the male cyclists. In the females, the respective genotypes for CC and CT were 5 (71.4%) and 2 (28.6%). C allele was counted as 12 (85.7%) and T allele as 2 (14.3%). Conclusion. In our cohort, both of the two genders, the CC genotype and C allele were found to be higher when compared to the other genotypes and T allele. Larger prospective studies focusing on the influence of MTHFR rs1801133 polymorphism in athletic performance are required for confirmation of our findings.