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Production of novel peptide-targeting antibodies for anti-Müllerian hormone receptor 2 and induction of cytotoxicity in ovarian cancer cells
Ovarian cancer is generally diagnosed at late stages. Monoclonal antibodies (MAbs) targeting antigens in ovarian cancer are used in the clinic. Anti-M & uuml;llerian hormone receptor type 2 (AMHR2) is a receptor highly expressed in ovarian cancer and it is a potential target antigen for immunotherapy. Extracellular domain of AMHR2 was analysed in terms of 3D structure and physicochemical properties, and 3 peptide sequences (Peptides 1, 7 and 11) were determined as targets. MAb production protocol was performed, and 6 MAb clones showing high affinity for peptides were obtained. P3B1, P10A10, P10B6 and P2A6 clones were for peptide 11 (P11), P2C9 was for P7, and P6C5 was for P1. Antibody isotype of P2A6 was IgG2a and the others were of IgG1 isotype. MAb binding to the native recombinant protein (AMHR2-Fc) was analysed by enzyme-linked immunosorbent assay (ELISA) and MAb binding to AMHR2 expressed by SKOV-3 ovarian cancer cells was analysed by western blot and immunofluorescent staining. P3B1 showed strong, P10A10, P10B6 and P2C9 showed medium affinity for the native protein (AMHR2-Fc). P3B1 and P2C9 showed strong binding in western blot analysis. Clones showed moderate binding in immunoflorescent staining. A complement dependent cytotoxicity (CDC) experiment was conducted using MAbs and transfected SKOV-3 cells. P3B1 induced a significant CDC. Variable regions of P3B1 MAb were sequenced. In conclusion, MAbs for three different regions of AMHR2 were produced. One clone was shown to induce cytotoxicity in ovarian cancer cells and its sequence was determined for future use as a humanised therapeutic MAb.Bilimsel Araştırma Projeleri, Erciyes ÜniversitesiThis work was supported by the Scientific and Technological Research Council of Turkey (TUB & Idot;TAK), Grant Number: 113S322 (C. SAKALAR) and Erciyes University Scientific Research Fund (EU- BAP), Grant Number: TOA- 2014- 4877 (C. SAKALAR). We thank Prof. Beyhan Cengiz for his suggestions on the manuscriptr No Statement Availabl
Fostering students’ multivariational reasoning through technology-enhanced learning environments
The study aimed to investigate students’ multivariational reasoning regarding the concept of two-variable functions in a technology-enhanced learning environment. This study provided two main contributions. The first was to identify students’ mental actions in multivariational reasoning through technology-enhanced learning environment, and the second was to how their mental actions evolve in this environment. The participants of the study involved 15 university students enrolled in a mathematics education programme. The data collection tools included audio and video recordings of students, screenshots, dynamic mathematics software GeoGebra files, and written products. The collected data were analysed based on the framework of mental actions of multivariational reasoning. As a result of the data analysis, it was found that the technology-enhanced learning environments encouraged students’ multivariational reasoning by supporting their processes of creating graphs of two-variable functions, mathematically interpreting contour lines, and interpreting the intersection of a plane with a surface function in three-dimensional space. The use of GeoGebra tools in the stages of collaborative learning, scientific debate, and self-reflection (ACODESA method) promoted students’ mental actions in reasoning about multivariation. © 2025 Informa UK Limited, trading as Taylor & Francis Group
Phytochemical profiling by UHPLC–ESI–MS/MS, in vitro antioxidant, in vivo antidiabetic, and pro-sexual effects of salvia balansae noë ex coss. flower extract in diabetic male rats
Our study assessed the phytochemical composition and the effects of Salvia balansae flower aqueous extract (FAE) on sexual dysfunction in diabetic rats. Total phenolic and flavonoid content, quantification of phytochemicals by ultrahigh performance liquid chromatography (UHPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) method, and in vitro antioxidant capacity of FAE extract were elucidated. For the in vivo study, diabetes was induced by one intraperitoneal injection of streptozotocin (STZ) (40 mg/kg), and treated diabetic rats were given FAE at 200 mg/kg. Rats were subjected to a sexual incentive motivation test (SIM) and a mating behavior test, and then serum testosterone levels and sperm quality were analyzed. Our study indicates that FAE contained a large amount of phenolic compounds and flavonoids, and 13 constituents were quantified; cynaroside (3.8 mg analyte/g extract) was the main compound, followed by rosmarinic acid (3.145 mg analyte/g extract), thus confirming its high antioxidant capacity. FAE treatment significantly reduced blood glucose levels, improved sexual motivation and copulatory behavior, increased testosterone levels, and enhanced sperm quality in diabetic-treated rats compared to diabetic untreated rats. The present work demonstrates the therapeutic potential of S. balansae flowers in enhancing reproductive function in diabetic rats, potentially through its antioxidant, antihyperglycemic, and aphrodisiac properties
A comparative study on magnetic solid phase extraction and magnetic colloidal gel based-dispersive solid phase extraction methods for preconcentration of carmoisine (E 122) in food samples
Magnetic solid phase extraction (M-SPE) and magnetic colloidal gel based-dispersive solid phase extraction (MCG-dSPE) methods have been developed with the Fe3O4@XAD-16 magnetic nanoparticle for preconcentration carmosine in some food samples. The effects of some parameters on preconcentration of carmoisine were investigated such as pH, amount of magnetic nanoparticle, volume of deep eutectic solvent (DES), type of desorption solvent, vortex time (for adsorption and desorption), sample volume and extraction time for both methods. Then, the recovery results of carmoisine for both methods were compared and satisfactory recoveries were obtained from the MCG-dSPE method. Under the optimum conditions for the MCG-dSPE method, the limit of detection (LOD) and limit of quantification (LOQ), preconcentration factor (PF) and enhancement factor (EF) were calculated as 0.86 mu g L-1 and 2.89 mu g L-1, 100, 103, respectively. All results showed that the developed method is a fast and good technique that can be applied to real samples for the determination of carmoisine
Clinical, biochemical and molecular characteristics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. Between 90% and 99% of cases of CAH are caused by 21-hydroxylase deficiency (21-OHD) caused by mutations in CYP21A2. Although 21-OHD has been historically divided into classical and non-classical forms, it is now thought to show a continuous phenotype. In the classical form, the external genitalia in females becomes virilized to varying degrees. If the disease is not recognized, salt wasting crises in the classical form may threaten life in neonates. Children experience accelerated somatic growth, increased bone age, and premature pubic hair in the simple virilizing form of classical 21-OHD. Female adolescents may present with severe acne, hirsutism, androgenic alopecia, menstrual irregularity or primary amenorrhea in the non-classical form. Diagnosis of CAH is made by clinical, biochemical and molecular genetic evaluation. In cases of 21-OHD, the diagnosis is based on the 17-hydroxyprogesterone (17-OHP) level being above 1000 ng/dL, measured early in the morning. In cases with borderline 17-OHP levels (200-1000 ng/dL), it is recommended to perform an adrenocorticotropic hormone (ACTH) stimulation test. Genotyping in cases with CAH should be performed if the adrenocortical profile is suspicious or if the ACTH stimulation test cannot be performed completely. After diagnosis, determining the carrier status of the parents and determining which parent the mutation was passed on from will help in interpreting the genetic results and determining the risk of recurrence in subsequent pregnancies
A case report of a new variant associated with vici syndrome in a Turkish infant; EPG5 frameshift variant
Introduction: Vici syndrome is a congenital multisystem disorder characterized primarily by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency, and oculocutaneous hypopigmentation, along with additional newly recognized findings. Autosomal recessive variants in the EPG5 gene, which encodes ectopic P-granules autophagy protein 5 (EPG5), a key regulator of autophagy, are known genetic causes of this syndrome. The aim of this case report is to present a novel disease-causing variant identified through EPG5 gene sequence analysis. Case Presentation: We report on a 2-month-old Turkish girl who presented with developmental delay, bilateral congenital cataracts, microcephaly, hypotonia, hypertrophic cardiomyopathy, hypopigmented skin lesions, and agenesis of the corpus callosum. Genetic analysis revealed a homozygous c.7504delC (p.G1n2502Argfs*4) frameshift variant in the EPG5 gene, which has not been previously documented. Conclusions: Adding a new variant to the literature is crucial, as it highlights the feasibility of reaching an accurate diagnosis through well-conducted physical examination findings in patients with early developmental delay. This case also raises awareness about such rare diseases. Moreover, recognizing new mutations is critical for understanding atypical findings, prognosis, treatment responses, and the genetic risks for other family members
The mediating role of negative attitudes toward menopause between benevolent sexist attitudes and irritability of perimenopausal women
The role of sexism in the menopausal process and symptoms has not been thoroughly investigated in the literature. In this context, we aim to test whether ambivalent sexism predicts irritability through negative attitudes toward menopause in perimenopausal women. Accordingly, 223 perimenopausal women (X̅age= 46.90) living in Turkey were included in the study sample. Our findings of the mediation analyses showed that negative attitudes toward menopause mediated the relationship between benevolent sexism (not hostile sexism) and irritability. Therefore, we suggested that benevolent sexism may have implicit and long-lasting negative effects on symptoms during perimenopause by instilling negative attitudes toward menopause, which is one of women’s developmental transitions. © 2025 Taylor & Francis Group, LLC
DC-link voltage stability enhancement in intermittent microgrids using coordinated reserve energy management strategy
In recent years, due to its cost effectiveness and environmental advantages, demand for renewable energy resources has grown and their contributions to grid power has therefore increased while requiring effective frequency and voltage regulation. DC link voltage instability is a potential problem in solar energy microgrids, especially during an intermittency, where the system reliability degrades and DC link capacitor is under higher stress. In this article, a novel reserve energy management scheme based on battery and super capacitor storage is presented to stabilize the DC link voltage and reduce capacitor stress, while enhancing the system reliability. The scheme is tested in four different scenarios: Inverter connected DC-microgrid with irradiance intermittencies, standalone DC-microgrid without inverter and irradiance intermittencies, standalone DC-microgrid without inverter and load intermittencies, and standalone DC-microgrid with inverter under irradiance intermittencies. Simulation results indicate that the proposed control strategy stabilizes DC link voltage over all scenarios, even subject to large instances of irradiance or load changes. During low solar irradiance, the battery and super-capacitor promote voltage stability by compensating power deficits from the utility grid in the inverter connected grid case. In stand alone mode, the battery provides power during intermittencies and the supercapacitor provides fast transient voltage compensation. The strategy is notable in reducing stress on DClink capacitors and mitigating inverter voltage fluctuations, ultimately enhancing inverter longevity. The results show that the proposed control scheme can improve voltage stability, mitigate the transient effects and guarantee the reliable operation of solar microgrids in variable conditions
Application of continuous wavelet transforms for simultaneous estimation of domperidone and lansoprazole in capsule formulations
UV–Vis spectroscopy remains essential in pharmaceutical research and quality control due to its accessibility, simplicity, and effectiveness. However, overlapping spectra resulting from multicomponent drug formulations present challenges. Here, we describe a signal processing strategy using continuous wavelet transform (CWT) to resolve overlapping spectra of domperidone (DMP) and lansoprazole (LSP) for simultaneous quantification. Three different wavelet functions (Symlets 3, Coiflets 1, Daubechies 10), were found to be suitable for this purpose. Linear calibration curves were constructed using the CWT zero-crossing technique and the methods were validated by analyzing a set of synthetic mixtures, intra-and inter-day samples, and standard addition samples. The assay results of commercial capsule samples were compared with those obtained by derivative spectroscopy, and no significant statistical difference was observed. The proposed CWT methods demonstrated good compliance with the label claims and proved to be reliable, versatile, fast, and cost-efficient analytical methods without the need for preliminary separation procedures.Chemometrics Laboratory of Ankara University Faculty of Pharmacy 10A333600
Seçili küresel hisse senedi piyasaları ile altın ve gümüş vadeli işlemleri arasındaki bağımlılık üzerine bir araştırma
Küreselleşme, ekonomik ve ticari pratiklerin dünya genelinde daha yüksek hacim ve frekansta uygulanabilmesine olanak tanımıştır. Bunun sonucunda sermaye yayılımlarının etki alanlarının genişlemesiyle, finansal piyasaların karşılıklı bağımlılıklarının arttığı söylenebilir. Ancak ekonomik krizler, salgın hastalıklar, savaşlar ve kontrolsüz göçler gibi olumsuz gelişmeler, piyasalar arasındaki ilişkilerin zayıflamasına ve anlamlı sayıda yatırımcının emtia yatırımlarına yönelmesine yol açmaktadır. Bu çalışmada; Sermaye Varlıkları Fiyatlandırma Modeli (CAPM), sistematik ve sistematik olmayan riskler karşısında seçilen finansal varlıkların beklenen getirilerinin değişeceği teoreminin seçilen piyasa verilerinin ilgili dönemde geçerli olup olmadığı araştırılmıştır. Çalışmanın amacı, altın ve gümüş vadeli işlem getirileri arasındaki olası eşbütünleşmeyi ve bunların seçilmiş küresel hisse senedi piyasaları getirileri üzerindeki etkisini zaman serisi analizleri ile incelemektir. Bu çalışmanın amacı; seçili küresel hisse senedi piyasaları ile altın ve gümüş vadeli işlemleri arasındaki muhtemel eşbütünleşme ilişkisinin zaman serisi analizleri ile incelenmesidir. 2014 Ocak ile 2024 Mayıs döneminde, seçili küresel hisse senedi endekslerinin aylık getirileri ile altın ve gümüş vadeli işlemleri aylık endeks getirileri arasındaki muhtemel ilişkiler Gecikmesi Dağıtılmış Otoregresif Sınır Testi (ARDL) Yöntemine göre incelenmiştir. Hata düzeltme katsayılarının hesaplanmasıyla, hisse senedi piyasaları ile emtia piyasaları arasındaki dengenin bozulması durumunda, dengenin ne kadarlık bir sürede yeniden sağlanabildiği tespit edilmiştir. Araştırmanın sonucunda altın ve gümüş vadeli işlemleri endeks getirileri ile seçili küresel hisse senedi endeks getirileri arasında uzun dönemli eşbütünleşme ilişkisinin var olduğu tespit edilmiştir. Seçili küresel endekslere ait getiriler ile altın ve gümüş vadeli işlemleri endeks getirileri arasındaki ilişkide kısa dönemde dengenin bozulması durumunda, altın vadeli işlemleri endeks getirileri için 0.9042 ay, gümüş vadeli işlemleri endeks getirileri için ise 0.6549 içinde dengenin yeniden sağlandığı tespit edilmiştir.Globalization has enabled greater volume and frequency of economic and commercial practices to be implemented worldwide. As a result, with the expansion of the scope of capital expansion, the interdependence of financial markets increases. However, negative developments such as economic crises, epidemics, wars, and uncontrolled migrations cause the relations between markets to weaken and a significant number of investors to turn to commodity investments. This study aims to evaluate the validity of the Capital Asset Pricing Model (CAPM) theorem, which posits that the expected returns of financial assets are influenced by systematic and unsystematic risks within the context of the selected market data for the specified period. Specifically, the study seeks to analyze the potential cointegration and the effects of gold and silver futures returns on the returns of selected global stock markets using time-series analysis. The potential relationships between the monthly returns of selected global stock indices and the monthly returns of gold and silver futures were analyzed for the period from January 2014 to May 2024 using the Autoregressive Distributed Lag (ARDL) Bound Test method. By calculating the error correction coefficients, it has been determined how long it takes to restore the balance in case the balance between the stock markets and commodity markets is disrupted. As a result of the research, it was determined that there is a long-term cointegration relationship between gold and silver futures index returns and selected global stock index returns. In the case of a short-term imbalance in the relationship between the yields of selected global indices and the index returns of gold and silver-term transactions, the balance was recovered within 0.9042 months for the index return of gold-term operations and 0.6549 months for the index return of silver-term operations