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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 Metadata only Dependence of erythrocyte deformability on mechanical stress and oxygenation(Federation amer Soc Exp Biol, 2017) N/A; N/A; N/A; Department of Physics; N/A; Yalçın, Özlem; Uğurel, Elif; Sağlam, Gökay; Erten, Ahmet Can; Aksu, Ali Cenk; Faculty Member; Researcher; Undergraduate Student; Teaching Faculty; PhD Student; Department of Physics; School of Medicine; School of Medicine; School of Medicine; College of Engineering; Graduate School of Health Sciences; 218440; N/A; N/A; N/A; N/AMechanical properties of erythrocytes are known to be affected by their oxygenation status. Several studies suggested that cytoskeletal rearrangements are carried out in an oxygen dependent manner. The structure of the cytoskeleton determines the mechanical properties of erythrocyte membrane. However, oxygen-dependent mechanical characteristics of erythrocyte are poorly studied whether oxygenated state could alter erythrocyte deformability. In this study, we investigated shear stress induced improvements in erythrocyte deformability through their oxygenation status. Venous blood was collected from male, healthy volunteers (n=10) between 25–50 ages. An informed written consent was obtained from each subject participated in the study according to Declaration of Helsinki. The hematocrit of blood samples adjusted to 0.4 l/l with autologous plasma. Whole blood samples were diluted with polyvinylpyrrolidone (PVP) solution (Mechatronics, Hoorn, Netherlands) with a dilution ratio of 1/200. Blood samples were equilibrated with either ambient air or nitrogen gas for at least 10 minutes at room temperature. Erythrocyte deformability was measured by a laser-assisted optical rotational cell analyzer (LORRCA MaxSis, Mechatronics, Netherlands) applying shear stresses (SS) ranging between 0.3 to 50 Pa. Then, a constant SS of 5, 10 and 20 Pa were applied continuously for 300 seconds and erythrocyte deformability was measured immediately afterwards. Maximal erythrocyte elongation index (EImax) and the SS required for one-half of this maximal deformation (SS1/2) were calculated by using the linear Lineweaver-Burke (LB) model. Deoxygenation of blood samples significantly decreased SS1/2 values both before and after SS applications (p < 0.001). EImax was significantly increased in deoxygenated blood before applying 5 Pa SS (p < 0.05). However, there were no significant differences after continuous SS in oxygenated and deoxygenated blood. Deoxygenation significantly decreased SS1/2/EImax values both before and after SS applications (p < 0.01). SS1/2/EImax values in both oxygenated and deoxygenated blood were significantly decreased after 5 and 10 Pa continuous SS applications although they were not significantly decreased after applying 20 Pa SS. Our study showed for the first time that erythrocyte deformability is improved in deoxygenated conditions in contrast to results presented in previous studies. This deformability improvement may control blood flow and consequently erythrocyte distribution within hypoxic tissues. Our study also demonstrated the relationship of oxygenation-deoxygenation shifts and magnitude of shear stress on erythrocyte deformability.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.Publication Metadata only Investigation of the effects of 50 Hz magnetic fields on platelet aggregation using a modified aggregometer(Taylor & Francis Inc, 2012) Sağdilek, Engin; Çelebi, Gürbüz; Department of Physics; Sebik, Oğuz; Researcher; Department of Physics; College of Sciences; N/APurpose: Electromagnetic fields have various effects on intracellular calcium levels, free oxygen radicals and various enzymes. The platelet activation pathway involves an increase in intracellular calcium levels and protein kinase C activation; and free oxygen radicals play a mediating role in this pathway. This study investigated whether 1 mT and 6 mT, 50 Hz magnetic fields had any effects on platelet aggregation. Materials and Methods: Blood from healthy volunteers was anticoagulated with either citrate or heparin. Each sample was divided in half and assigned to exposure and control groups. Platelet rich plasma samples in the exposure group were exposed to a 1 mT or a 6 mT, 50 Hz magnetic field for 1.5 or 1 h, respectively. The samples from both exposure and control groups were simultaneously evaluated using a modified optical aggregometer. Adenosine-diphosphate, collagen, and epinephrine were used as inducing agents. The slopes of the aggregation curve, the maximum values and the areas under the curves were recorded and compared. Results: A significant effect was observed only in the 1 mT-citrate group. It was found that magnetic field exposure significantly increased the maximum values and slopes of the collagen-induced aggregations. Conclusions: It was found that magnetic field exposure has an activating effect on platelet aggregation.Publication Metadata only Large-scale orientational order in bacterial colonies during inward growth(Elife Sciences Publ Ltd, 2022) Vetter, Roman; Department of Physics; Department of Electrical and Electronics Engineering; Department of Physics; N/A; Yaman, Yusuf İlker; Yüce, Tevfik Can; Kocabaş, Aşkın; Başaran, Mustafa; Other; Undergraduate Student; Faculty Member; Master Student; Department of Electrical and Electronics Engineering; Department of Physics; College of Sciences; College of Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; 227753; N/ADuring colony growth, complex interactions regulate the bacterial orientation, leading to the formation of large-scale ordered structures, including topological defects, microdomains, and branches. These structures may benefit bacterial strains, providing invasive advantages during colonization. Active matter dynamics of growing colonies drives the emergence of these ordered structures. However, additional biomechanical factors also play a significant role during this process. Here, we show that the velocity profile of growing colonies creates strong radial orientation during inward growth when crowded populations invade a closed area. During this process, growth geometry sets virtual confinement and dictates the velocity profile. Herein, flow-induced alignment and torque balance on the rod-shaped bacteria result in a new stable orientational equilibrium in the radial direction. Our analysis revealed that the dynamics of these radially oriented structures, also known as aster defects, depend on bacterial length and can promote the survival of the longest bacteria around localized nutritional hotspots. The present results indicate a new mechanism underlying structural order and provide mechanistic insights into the dynamics of bacterial growth on complex surfaces.Publication Open Access Terminal neuron localization to the upper cortical plate is controlled by the transcription factor NEUROD2(Nature Publishing Group (NPG), 2019) Department of Molecular Biology and Genetics; Department of Physics; Akkaya, Cansu; Atak, Dila; Güzelsoy, Gizem; Dunn, Cory David; Dunn, Gülayşe İnce; Kabakçıoğlu, Alkan; Master Student; Faculty Member; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Physics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; N/A; 105301; N/A; 49854Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Cortical layers appear after a highly regulated migration process in which cells move from the deeper, proliferative zone toward the superficial layers. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular localization within the cortical plate. In mice, in utero knockdown of Neurod2 resulted in reduced numbers of neurons localized to the uppermost region of the developing cortex, also termed the primitive cortical zone. Our ChIP-Seq and RNA-Seq analyses of genes regulated by NEUROD2 in the developing cortex identified a number of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migration. Our focused analysis of regulation of the Reln gene, encoding the extracellular ligand REELIN, uncovered NEUROD2 binding to conserved E-box elements in multiple introns. Furthermore, we demonstrate that knockdown of NEUROD2 in primary cortical neurons resulted in a strong increase in Reln gene expression at the mRNA level, as well as a slight upregulation at the protein level. These data reveal a new role for NEUROD2 during the late stages of neuronal migration, and our analysis of its genomic targets offers new genes with potential roles in cortical lamination.