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Publication Metadata only 3D ultrasound assessment of effect of controlled ovarian stimulation on endometrioma volume(Oxford University Press (OUP), 2016) Seyhan, A.; Balaban, B.; Urman, Cumhur Bülent; Ata, Mustafa Barış; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 12147; 232576N/APublication Metadata only A Bayesian generalized linear model for Crimean–Congo hemorrhagic fever incidents(Springer, 2018) Ryu, Duchwan; Bilgili, Devrim; Liang, Faming; Ebrahimi, Nader; Ergönül, Önder; Faculty Member; School of Medicine; 110398Global spread of the Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection disease found in parts of Africa, Asia, Eastern Europe and Middle East, with a fatality rate of up to 30%. A timely prediction of the prevalence of CCHF incidents is highly desirable, while CCHF incidents often exhibit nonlinearity in both temporal and spatial features. However, the modeling of discrete incidents is not trivial. Moreover, the CCHF incidents are monthly observed in a long period and take a nonlinear pattern over a region at each time point. Hence, the estimation and the data assimilation for incidents require extensive computations. In this paper, using the data augmentation with latent variables, we propose to utilize a dynamically weighted particle filter to take advantage of its population controlling feature in data assimilation. We apply our approach in an analysis of monthly CCHF incidents data collected in Turkey between 2004 and 2012. The results indicate that CCHF incidents are higher at Northern Central Turkey during summer and that some beforehand interventions to stop the propagation are recommendable. Supplementary materials accompanying this paper appear on-line.Publication Metadata only A comprehensive comparative transcriptional and translational analyses of the impact of ovarian response type, stimulation protocol and mode of trigger on the luteal function(Elsevier Science Inc, 2018) Seyhan, A; Yakın, Kayhan; Ata, Mustafa Barış; Öktem, Özgür; Bildik, Gamze; Urman, Cumhur Bülent; Faculty Member; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 106822; 182910; 102627; N/A; 12147Objective: We aimed to compare molecular characteristics of the luteal granulosa cells between natural vs. stimulated IVF cycles in good and poor-responders. Design: Translational research study. Materials and Methods: Luteinized granulosa cells were obtained from good (n=154) and poor responder (n=64) IVF patients comparable for age, type and dose of gonadotropin and IVF etiology. Good-responders (4-15 oocytes) underwent natural (n=22), GnRH agonist (long protocol n=44) and antagonist IVF cycles triggered with rec-hCG (n=46) or GnRH agonist leuprolide acetate (n=42). Poor-responders fulfilling the Bologna criteria consisted of 64 patients undergoing GnRH antagonist protocol triggered with hCG (n=36) or hCG+GnRH agonist (n=28). Results: In the good-responders, natural cycle (NC) granulosa cells were significantly more viable (88%) compared to the stimulated IVF cycles (66%, 64% and 37% for agonist and antagonist cycles triggered with hCG and agonist respectively, p<0.05). The mRNA expression of steroidogenic enzymes (SCC, stAR, 3B-HSD, 17B-HSD and aromatase), LH receptor and VEGF and in vitro E2 and P productions were comparable between hCG-triggered agonist and antagonist cycles, but significantly higher than NC in the first days of culture. However, on the following days their hormone productions and viability began to decline very rapidly with the most drastic decrease being observed in the agonist triggered cycles. By contrast, NC granulosa cells maintained their viability and produced E 2 and P in increasing amounts in culture up to six days. The expression of anti-apoptotic genes (AKT-1, BCL2-L2) were significantly lower, and pro-apoptotic genes (BAD, BID, BAX, Cas3) were significantly higher in the stimulated cycles particularly in the agonist triggered ones compared to NC granulosa cells. Pulse exposure to cisplatin induced apoptosis only in a small fraction of the cells from the NCs whereas the same exposure caused massive apoptosis in the cells of the stimulated cycles (27% vs. 78% respectively, p<0.01). In the poor-responders both viability and steroidogenic activity of the cells were more severely reduced compared to the antagonist cycles of the good-responders. There were no significant differences between hCG and hCG+agonist triggered cycles in terms of viability, hormone production, VEGF and LH receptor expressions in the luteal granulosa cells. Conclusions Reduced survival and increased apoptosis of luteal granulosa cells leading to defective steroid production in stimulated cycles in comparison to natural ones may at least in part explain why luteal phase is defective and requires exogenous P supplementation for support in these cycles. Also dual trigger does not appear to improve luteal function in the poor-responders.Publication Open Access A disconnect between upslope shifts and climate change in an Afrotropical bird community(Wiley, 2020) Neate-Clegg, Montague H. C.; O'Brien, Timothy G.; Mulindahabi, Felix; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589Climate change threatens to push species to higher elevations and eventual extinction. Birds, in particular, are shown to be shifting upslope in the Neotropics and Southeast Asia. Yet previous studies have lacked the temporal resolution to investigate distributional dynamics over time in relation to climatic fluctuations, especially in the understudied Afrotropics. Here, we used 15 years of point-count data from across an elevational gradient (1,767-2,940 m) in Rwanda, to assess elevational shift rates and dynamics in a community of Afrotropical birds. In general, species shifted their elevations upslope by 1.9 m/year, especially at their lower elevational limits which shifted by 4.4 m/year. Importantly, these shifts occurred despite the fact that local temperature and precipitation showed little trend over the study period. Moreover, the interannual distributions of few species were associated with temperature, suggesting that temperature played little direct role in determining elevational distributions of birds. Instead, upslope shifts may be more related to incremental shifts in habitat and resources which lag behind decades of increased temperature in the region. Precipitation appeared to have more of an effect than temperature in determining interannual elevational changes, allowing species to expand their ranges in years of higher rainfall. Our results highlight the need to understand the mechanisms driving upslope shifts as they occur throughout the tropics. It will be critical for montane regions of the tropics to preserve contiguous blocks of forest across elevational gradients to allow wildlife to shift unimpeded.Publication Open Access A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability(eLife Sciences Publications, 2018) Chia, Poh Hui; Zhong, Franklin Lei; Niwa, Shinsuke; Bonnard, Carine; Utami, Kagistia Hana; Zhang, Ruizhu; Lee, Hane; Eskin, Ascia; Nelson, Stanley F.; Xie, William H.; Al-Tawalbeh, Samah; El-Khateeb, Mohammad; Shboul, Mohammad; Pouladi, Mahmoud A.; Al-Raqad, Mohammad; N/A; Reversade, Bruno; Faculty Member; School of MedicineCalcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in CAMK2A. The missense mutation, p. His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme.ln vivo, CAMK2A(H477Y) failed to rescue neuronal defects in C. elegans lacking unc-43, the ortholog of human CAMK2A. In vitro, neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in CAMK2A leads to neurodevelopmental defects in humans and suggest that dysfunctional CAMK2 paralogs may contribute to other neurological disorders.Publication Metadata only A novel and simple method to schedule GNRH antagonist cycles with a short course of oral estradiol in the early follicular phase(Oxford Univ Press, 2019) Angun, B.; Türkgeldi, Engin; Yıldız, Şule; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 329649; 134205; 182910N/APublication Metadata only A novel flexible progestin primed ovarian stimulatıon protocol: Comparıson of pregnancy outcomes with the flexible GnRH antagonist protocol in an oocyte donation program(Oxford Univ Press, 2019) Angun, B.; N/A; Yıldız, Şule; Türkgeldi, Engin; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 134205; 329649; 182910N/APublication Metadata only A survey of women who cryopreserved oocytes for non-medical indications(Elsevier Science Inc, 2017) N/A; N/A; N/A; N/A; Ata, Ayşe Seyhan; Akın, Öznur Dündar; Urman, Cumhur Bülent; Yakın, Kayhan; Doctor; Doctor; Faculty Member; Faculty Member; N/A; N/A; School of Medicine; School of Medicine; American Hospital; N/A; N/A; 12147; 106822Objective: What are the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation? Design: All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty three women were invited to participate in a survey at least 6 months after completion of the treatment cycle. Materials and Methods: Eigthy-one patients completed the survey.All women were given personalized counselling before starting the treatment cycle. Counselling included, chances of natural conception at a given age and the concept of ovarian reserve. The questionnaire investigated initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. Results: The mean (± standard deviation) age at the time of oocyte freezing was 38.5 ± 2.68 years. The average number (min - max) of mature oocytes cryopreserved was 5.48 ± 6.6 (1-16). Two major motivations were absence of a male partner at the time of decision (40%) and an anticipated age-related fertility decline (42%). Majority of women (42%) opted to limit the use of cryopreserved oocytes up to the age of 45, and 51% of bankers wished that they had completed their family by the age of 35. 41% of the women told that they would donate their oocytes for research, 35% discard, and 24% donate to other infertile couples, if they did not use for own reproduction. 54% of patients thought that they did not have an adequate number of stored oocytes, 43 % wanted to do another cycle. 59% of the latter, were not able to undergo another cycle since they couldn’t afford another cycle. 42% and 35% of the women reported anxiety and injections, respectively, as the most challenging factor during treatment. Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35-39 but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend and 72% felt more secure in terms of reproductive potential. Conclusions: Despite comprehensive personalized counselling prior to the start of ovarian stimulation, many women, as well as some health care policy makers do not seem to have a realistic understanding of reproductive ageing. Overestimaing effectiveness of assisted reproductive technology and arbitrarily delaying childbearing can lead to future childlessnes. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security. Increasing awareness and knowledge about reproductive ageing is needed.Publication Metadata only A survey of women who cryopreserved oocytes for non-medical indications (social fertility preservation)(Springer, 2021) Akin, Öznur Dündar; Ertaş, Sinem; N/A; N/A; N/A; N/A; Ata, Ayşe Seyhan; Ata, Mustafa Barış; Yakın, Kayhan; Urman, Cumhur Bülent; Doctor; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; School of Medicine; School of Medicine; American Hospital; School of Medicine; N/A; N/A; N/A; 182910; 106822; 12147To evaluate the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation. Cohort survey study was conducted at an academic medical center. All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty-three women were contacted by phone to participate in a survey. The questionnaire investigated the initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. The mean age at the time of oocyte freezing was 38.5 +/- 2.68 years. The average number of mature oocytes cryopreserved was 5.48 +/- 6.6 (1-16). Two major motivations were absence of a male partner (40%) and an anticipated age-related fertility decline (42%). Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35 and 39, but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend, and 72% felt more secure in terms of reproductive potential. Despite comprehensive personalized counseling prior to the start of ovarian stimulation, many women do not seem to have a realistic understanding of reproductive aging. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security.Publication Open Access Acute inhibition of centriolar satellite function and positioning reveals their functions at the primary cilium(Public Library of Science, 2020) Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; 206349Centriolar satellites are dynamic, membraneless granules composed of over 200 proteins. They store, modify, and traffic centrosome and primary cilium proteins, and help to regulate both the biogenesis and some functions of centrosomes and cilium. In most cell types, satellites cluster around the perinuclear centrosome, but their integrity and cellular distribution are dynamically remodeled in response to different stimuli, such as cell cycle cues. Dissecting the specific and temporal functions and mechanisms of satellites and how these are influenced by their cellular positioning and dynamics has been challenging using genetic approaches, particularly in ciliated and proliferating cells. To address this, we developed a chemical-based trafficking assay to rapidly and efficiently redistribute satellites to either the cell periphery or center, and fuse them into stable clusters in a temporally controlled way. Induced satellite clustering at either the periphery or center resulted in antagonistic changes in the pericentrosomal levels of a subset of proteins, revealing a direct and selective role for their positioning in protein targeting and sequestration. Systematic analysis of the interactome of peripheral satellite clusters revealed enrichment of proteins implicated in cilium biogenesis and mitosis. Importantly, induction of peripheral satellite targeting in ciliated cells revealed a function for satellites not just for efficient cilium assembly but also in the maintenance of steady-state cilia and in cilia disassembly by regulating the structural integrity of the ciliary axoneme. Finally, perturbing satellite distribution and dynamics inhibited their mitotic dissolution, and mitotic progression was perturbed only in cells with centrosomal satellite clustering. Collectively, our results for the first time showed a direct link between satellite functions and their pericentrosomal clustering, suggested new mechanisms underlying satellite functions during cilium assembly, and provided a new tool for probing temporal satellite functions in different contexts