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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 Avian responses to selective logging shaped by species traits and logging practices(The Royal Society, 2015) Burivalova, Zuzana; Lee, Tien Ming; Giam, Xingli; Wilcove, David S.; Koh, Lian Pin; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589Selective logging is one of the most common forms of forest use in the tropics. Although the effects of selective logging on biodiversity have been widely studied, there is little agreement on the relationship between life-history traits and tolerance to logging. In this study, we assessed how species traits and logging practices combine to determine species responses to selective logging, based on over 4000 observations of the responses of nearly 1000 bird species to selective logging across the tropics. Our analysis shows that species traits, such as feeding group and body mass, and logging practices, such as time since logging and logging intensity, interact to influence a species' response to logging. Frugivores and insectivores were most adversely affected by logging and declined further with increasing logging intensity. Nectarivores and granivores responded positively to selective logging for the first two decades, after which their abundances decrease below pre-logging levels. Larger species of omnivores and granivores responded more positively to selective logging than smaller species from either feeding group, whereas this effect of body size was reversed for carnivores, herbivores, frugivores and insectivores. Most importantly, species most negatively impacted by selective logging had not recovered approximately 40 years after logging cessation. We conclude that selective timber harvest has the potential to cause large and long-lasting changes in avian biodiversity. However, our results suggest that the impacts can be mitigated to a certain extent through specific forest management strategies such as Llengthening the rotation cycle and implementing reduced impact logging.Publication Metadata only Bayesian framework for parametric bivariate accelerated lifetime modeling and its application to hospital acquired infections(Wiley, 2016) Bilgili, D.; Ryu, D.; Ebrahimi, N; Ergönül, Önder; Faculty Member; School of Medicine; 110398Infectious diseases that can be spread directly or indirectly from one person to another are caused by pathogenic microorganisms such as bacteria, viruses, parasites, or fungi. Infectious diseases remain one of the greatest threats to human health and the analysis of infectious disease data is among the most important application of statistics. In this article, we develop Bayesian methodology using parametric bivariate accelerated lifetime model to study dependency between the colonization and infection times for Acinetobacter baumannii bacteria which is leading cause of infection among the hospital infection agents. We also study their associations with covariates such as age, gender, apache score, antibiotics use 3 months before admission and invasive mechanical ventilation use. To account for singularity, we use Singular Bivariate Extreme Value distribution to model residuals in Bivariate Accelerated lifetime model under the fully Bayesian framework. We analyze a censored data related to the colonization and infection collected in five major hospitals in Turkey using our methodology. The data analysis done in this article is for illustration of our proposed method and can be applied to any situation that our model can be used.Publication Metadata only Bone morphogenetic protein-7 (BMP-7) reduces E2 and P4 production of human luteinized granulosa cells by down-regulating the expression of the steroidogenic enzymes StAR and 3B-HSD(Oxford Univ Press, 2021) Öktem, Özgür; N/A; Faculty Member; Graduate School of Health Sciences; School of Medicine; N/A; 102627Study Question: What is the biological role of BMP–7 on the granulosa cells after luteinization? Summary Answer: BMP–7 down regulates the steroidogenic enzymes and reduces E2 and P4 output of luteinized granulosa cells. What is Known Already: BMP–7 is a member of TGF-B super family that is mainly produced by theca cells in the ovary. It promotes the transition of primordials into primary follicles, and the growth and preantral and antral follicles, and inhibits progesterone (P4) production during FSH-induced growth phase of Graafian follicles (luteinization inhibitor). However, limited data is available regarding the role of this hormone on the molecular luteal characteristics of granulosa cells after ovulation and luteinization processes. We therefore aimed to address this issue in the current study. Study Design, Size, Duration: A basic science study on the corpus luteum biology. Participants/Materials, Setting, Methods: Human luteal granulosa cells were obtained from 10 normo-responder IVF patients undergoing ovarian stimulation with rec-FSH and GnRH antagonist protocol and cultured with recombinant forms of BMP–7, hCG and activin-A for 24h. The presence of cognate receptors for these hormones were validated using RT-PCR. The expression of the steroidogenic enzymes were analyzed with quantitative immunoblotting, real-time RT-PCR and confocal microscopy. E2 and P4 production of the cells were measured using ECLIA method. Main Results and the Role of Chance: BMP–7 significantly down-regulated the expression of StAR and 3b-HSD in immunoblotting and confocal images and caused a substantial decrease in P4 production in the luteal GCs in a dose dependent manner. It did not cause any notable change in aromatase expression, however E2 output declined in parallel with P4 due to the reduced expression of StAR, which is the rate limiting enzyme in steroidogenesis. hCG significantly up-regulated StAR and 3b-HSD expression and enhanced P4 output whereas activin-A did the opposite effect. Viability assay with Yo-PRO–1 uptake assay did not reveal any significant differences in the viability of the cells before and after treatment with these hormones. Limitations, Reasons for Caution: In-vitro findings requires validation using in-vivo models. Wider Implications of the Findings: Reversal of luteinization and down-regulation of steroidogenesis with BMP–7 and other hormones with similar actions warrant further investigation to test their in-vivo effects in order to develop new strategies against ovarian hyperstimulation syndrome (OHSS).Publication Metadata only Comparison of two intraoperative examination methods for the diagnosis of sentinel lymph node metastasis in clinically early stage endometrial cancer: a Turkish Gynecologic Oncology Group Study (TRSGO-SLN-003)(Elsevier, 2021) Taskin, Salih; Varli, Bulut; Altin, Duygu; Takmaz, Ozguc; Ersoz, Cevriye Cansiz; Turan, Hasan; Zeren, Handan; Havare, Semiha Battal; Karabuk, Emine; Naki, Murat; Gungor, Mete; Kose, Faruk; Ortac, Firat; Arvas, Macit; Ayhan, Ali; N/A; Vatansever, Doğan; Taşkıran, Çağatay; Bulutay, Pınar; Faculty Member; Faculty Member; Teaching Faculty; School of Medicine; School of Medicine; School of Medicine; 193687; 134190; 133565Objective: This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. Study Design: Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. Results: Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. Conclusion: Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.Publication Metadata only Conservation of migratory species(Cell Press, 2018) Horns, Joshua J.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589N/APublication Metadata only Dealing with repetitions in sequencing by hybridization(Elsevier, 2006) Blazewicz, Jacek; Glover, Fred; Kasprzak, Marta; Markiewicz, Wojciech T.; Rebholz-Schuhmann, Dietrich; Swiercz, Aleksandra; Department of Industrial Engineering; Oğuz, Ceyda; Faculty Member; Department of Industrial Engineering; College of Engineering; 6033DNA sequencing by hybridization (SBH) induces errors in the biochemical experiment. Some of them are random and disappear when the experiment is repeated. Others are systematic, involving repetitions in the probes of the target sequence. A good method for solving SBH problems must deal with both types of errors. In this work we propose a new hybrid genetic algorithm for isothermic and standard sequencing that incorporates the concept of structured combinations. The algorithm is then compared with other methods designed for handling errors that arise in standard and isothermic SBH approaches. DNA sequences used for testing are taken from GenBank. The set of instances for testing was divided into two groups. The first group consisted of sequences containing positive and negative errors in the spectrum, at a rate of up to 20%, excluding errors coming from repetitions. The second group consisted of sequences containing repeated oligonucleotides, and containing additional errors up to 5% added into the spectra. Our new method outperforms the best alternative procedures for both data sets. Moreover, the method produces solutions exhibiting extremely high degree of similarity to the target sequences in the cases without repetitions, which is an important outcome for biologists.Publication Open Access Distinct chemical composition and enzymatic treatment induced human endothelial cells survival in acellular ovine aortae(BioMed Central, 2021) Rahbarghazi, Reza; Saberianpour, Shirin; Delkhosh, Aref; Amini, Hassan; Hassanpour, Mehdi; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 163024Objective: the current experiment aimed to assess the impact of detergents such as 3% Triton X-100, 1% peracetic acid, 1% Tween-20, and 1% SDS in combination with Trypsin–EDTA on acellularization of ovine aortae after 7 days. Results: Hematoxylin–Eosin staining showed an appropriate acellularization rate in ovine aortae, indicated by a lack of cell nuclei in the tunica media layer. DAPI staining confirmed the lack of nuclei in the vascular wall after being exposed to the combination of chemical and enzymatic solutions. Verhoeff-Van Gieson staining showed that elastin fibers were diminished in acellular samples compared to the control group while collagen stands were unchanged. CCK-8 survival assay showed enhanced viability in human umbilical vein endothelial cells 5 days after being cultured on decellularized samples compared to the cells cultured on a plastic surface (p < 0.05). SEM imaging showed flattening of endothelial cells on the acellular surface.Publication Metadata only Does the magnetic field of a magnetic stirrer in an optical aggregometer affect concurrent platelet aggregation?(2013) Sağdilek, Engin; Çelebi, Gürbüz; Department of Physics; Sebik, Oğuz; Researcher; Department of Physics; College of Sciences; N/APlatelets are subjected to extremely low frequency electromagnetic fields during standard aggregometry measurements owing to the use of a magnetic stir bar in the instrument. This study evaluates the effects of this magnetic field exposure on platelet aggregation by comparing the results obtained in a modified aggregometer. Blood samples from healthy volunteers were anticoagulated using citrate or heparin. Platelet-rich plasma (PRP) samples were prepared. A mechanical stirring device was attached to the aggregometer instead of the magnetic stir bar system. The PRP samples were stirred using a stirring rod tip that did not produce any magnetic fields in one channel of the aggregometer; in the other channel, a stirring rod carrying a small magnet at its tip was used. As a result, a magnetic field in the extremely low frequency range and in the amplitude range of 1.9–65 mT was applied to the platelets assigned to the channel where the magnetic stirring rod tip was used. Aggregation was induced using adenosine diphosphate (ADP), collagen, or epinephrine. The slopes, maximum aggregation values, and areas under the aggregation curves were compared between the magnetic and neutral stirring rod tip groups. For samples stirred with the magnetic stirring rod tip, a significant decrease was observed in 12 of the 14 parameters evaluated for aggregations induced with ADP or collagen compared to the neutral stirring rod tip, regardless of the method used for anticoagulation. This observation indicates that the magnetic stir bars used in standard aggregometry may significantly alter aggregation parameters and platelets may be possible targets of electromagnetic fields.