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Publication 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 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 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 contextsPublication Metadata only Adaptive tracking algorithm for trajectory analysis of cells and layer-by-layer assessment of motility dynamics(Pergamon-Elsevier Science Ltd, 2022) Bayraktar, Halil; N/A; Department of Molecular Biology and Genetics; Qureshi, Mohammad Haroon; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Graduate School of Sciences and Engineering; College of Sciences; N/A; 105301Tracking biological objects such as cells or subcellular components imaged with time-lapse microscopy enables us to understand the molecular principles about the dynamics of cell behaviors. However, automatic object detection, segmentation and extracting trajectories remain as a rate-limiting step due to intrinsic challenges of video processing. This paper presents an adaptive tracking algorithm (Adtari) that automatically finds the op-timum search radius and cell linkages to determine trajectories in consecutive frames. A critical assumption in most tracking studies is that displacement remains unchanged throughout the movie and cells in a few frames are usually analyzed to determine its magnitude. Tracking errors and inaccurate association of cells may occur if the user does not correctly evaluate the value or prior knowledge is not present on cell movement. The key novelty of our method is that minimum intercellular distance and maximum displacement of cells between frames are dynamically computed and used to determine the threshold distance. Since the space between cells is highly variable in a given frame, our software recursively alters the magnitude to determine all plausible matches in the trajectory analysis. Our method therefore eliminates a major preprocessing step where a constant distance was used to determine the neighbor cells in tracking methods. Cells having multiple overlaps and splitting events were further evaluated by using the shape attributes including perimeter, area, ellipticity and distance. The features were applied to determine the closest matches by minimizing the difference in their magnitudes. Finally, reporting section of our software were used to generate instant maps by overlaying cell features and trajectories. Adtari was validated by using videos with variable signal-to-noise, contrast ratio and cell density. We compared the adaptive tracking with constant distance and other methods to evaluate performance and its efficiency. Our algorithm yields reduced mismatch ratio, increased ratio of whole cell track, higher frame tracking efficiency and allows layer-by-layer assessment of motility to characterize single-cells. Adaptive tracking provides a reliable, accurate, time efficient and user-friendly open source software that is well suited for analysis of 2D fluorescence microscopy video datasets.Publication Metadata only Anomalies in the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae(Elsevier, 2010) N/A; Department of Physics; Tuğrul, Murat; Kabakçıoğlu, Alkan; N/A; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854We investigate the structural and dynamical properties of the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae and compare it with two "unbiased" ensembles: one obtained by reshuffling the edges and the other generated by mimicking the transcriptional regulation mechanism within the cell. Both ensembles reproduce the degree distributions (the first-by construction-exactly and the second approximately), degree-degree correlations and the k-core structure observed in Yeast. An exceptionally large dynamically relevant core network found in Yeast in comparison with the second ensemble points to a strong bias towards a collective organization which is achieved by subtle modifications in the network's degree distributions. We use a Boolean model of regulatory dynamics with various classes of update functions to represent in vivo regulatory interactions. We find that the Yeast's core network has a qualitatively different behavior, accommodating on average multiple attractors unlike typical members of both reference ensembles which converge to a single dominant attractor. Finally, we investigate the robustness of the networks and find that the stability depends strongly on the used function class. The robustness measure is squeezed into a narrower band around the order-chaos boundary when Boolean inputs are required to be nonredundant on each node. However, the difference between the reference models and the Yeast's core is marginal, suggesting that the dynamically stable network elements are located mostly on the peripherals of the regulatory network. Consistently, the statistically significant three-node motifs in the dynamical core of Yeast turn out to be different from and less stable than those found in the full transcriptional regulatory network.Publication Open Access Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication(Nature Portfolio, 2021) Yurtman, Erinç; Özer, Onur; Yüncü, Eren; Dağtaş, Nihan Dilşad; Koptekin, Dilek; Çakan, Yasin Gökhan; Özkan, Mustafa; Akbaba, Ali; Kaptan, Damla; Atağ, Gözde; Vural, Kıvılcım Başak; Gündem, Can Yümni; Martin, Louise; Kılınç, Gülşah Merve; Ghalichi, Ayshin; Açan, Sinan Can; Yaka, Reyhan; Sağlıcan, Ekin; Lagerholm, Vendela Kempe; Krzewinska, Maja; Gunther, Torsten; Miranda, Pedro Morell; Pişkin, Evangelia; Sevketoğlu, Müge; Bilgin, C. Can; Atakuman, Ciğdem; Erdal, Yılmaz Selim; Sürer, Elif; Altınışık, N. Ezgi; Lenstra, Johannes A.; Yorulmaz, Sevgi; Abazari, Mohammad Foad; Hoseinzadeh, Javad; Baird, Douglas; Bıcakcı, Erhan; Çevik, Özlem; Gerritsen, Fokke; Gotherstrom, Anders; Somel, Mehmet; Togan, İnci; Özer, Füsun; Department of Archeology and History of Art; Özbal, Rana; Faculty Member; Department of Archeology and History of Art; College of Social Sciences and Humanities; 55583Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.Publication Metadata only Are signals of aggressive intent less honest in urban habitats?(Oxford Univ Press Inc, 2020) Beck, Michelle L.; Sewall, Kendra B.; Department of Psychology; Akçay, Çağlar; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 272053How anthropogenic change affects animal social behavior, including communication is an important question. Urban noise often drives shifts in acoustic properties of signals but the consequences of noise for the honesty of signals-that is, how well they predict signaler behavior-is unclear. Here we examine whether honesty of aggressive signaling is compromised in male urban song sparrows (Melospiza melodia). Song sparrows have two honest close-range signals: the low amplitude soft songs (an acoustic signal) and wing waves (a visual signal), but whether the honesty of these signals is affected by urbanization has not been examined. If soft songs are less effective in urban noise, we predict that they should predict attacks less reliably in urban habitats compared to rural habitats. We confirmed earlier findings that urban birds were more aggressive than rural birds and found that acoustic noise was higher in urban habitats. Urban birds still sang more soft songs than rural birds. High rates of soft songs and low rates of loud songs predicted attacks in both habitats. Thus, while urbanization has a significant effect on aggressive behaviors, it might have a limited effect on the overall honesty of aggressive signals in song sparrows. We also found evidence for a multimodal shift: urban birds tended to give proportionally more wing waves than soft songs than rural birds, although whether that shift is due to noise-dependent plasticity is unclear. These findings encourage further experimental study of the specific variables that are responsible for behavioral change due to urbanization.Publication Metadata only Audible pain squeaks can mediate emotional contagion across pre-exposed rats with a potential effect of auto-conditioning(Nature Portfolio, 2023) Packheiser, Julian; Paradiso, Enrica; Michon, Frederic; Ramaaker, Eline; Sahin, Neslihan; Muralidharan, Sharmistha; Woehr, Markus; Gazzola, Valeria; Keysers, Christian; Department of Psychology; Soyman, Efe; Department of Psychology; College of Social Sciences and HumanitiesFootshock self-experience enhances rodents' reactions to the distress of others. Here, we tested one potential mechanism supporting this phenomenon, namely that animals auto-condition to their own pain squeaks during shock pre-exposure. In Experiment 1, shock pre-exposure increased freezing and 22 kHz distress vocalizations while animals listened to the audible pain-squeaks of others. In Experiment 2 and 3, to test the auto-conditioning theory, we weakened the noxious pre-exposure stimulus not to trigger pain squeaks, and compared pre-exposure protocols in which we paired it with squeak playback against unpaired control conditions. Although all animals later showed fear responses to squeak playbacks, these were weaker than following typical pre-exposure (Experiment 1) and not stronger following paired than unpaired pre-exposure. Experiment 1 thus demonstrates the relevance of audible pain squeaks in the transmission of distress but Experiment 2 and 3 highlight the difficulty to test auto-conditioning: stimuli weak enough to decouple pain experience from hearing self-emitted squeaks are too weak to trigger the experience-dependent increase in fear transmission that we aimed to study. Although our results do not contradict the auto-conditioning hypothesis, they fail to disentangle it from sensitization effects. Future studies could temporarily deafen animals during pre-exposure to further test this hypothesis. While audible pain squeaks among rats are relevant in the transmission of distress, it is difficult to disentangle whether animals can be auto-conditioned to the sound of their own pain squeaks.