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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Virulence determinants of colistin-resistant K. pneumoniae high-risk clones(Multidisciplinary Digital Publishing Institute (MDPI), 2021) Department of Industrial Engineering; Department of Industrial Engineering; Ergönül, Önder; Gönen, Mehmet; Can, Füsun; Doğan, Özlem; Vatansever, Cansel; Ataç, Nazlı; Albayrak, Özgür; Karahüseyinoğlu, Serçin; Şahin, Özgün Ekin; Kılıçoğlu, Bilge Kaan; Demiray, Atalay; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Undergraduate Student; Researcher; Faculty Member; Master Student; School of Medicine; Graduate School of Health Sciences; College of Engineering; 110398; 237468; 103165; 170418; N/A; N/A; N/A; 110772; N/A; N/A; N/AWe proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p <= 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p = 0.024), kfu (OR:27.0; CI: 5.67-179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.Publication Open Access Genome-wide analysis reveals regional patterns of drift, structure, and gene flow in longfin smelt (Spirinchus thaleichthys) in the northeastern Pacific(Canadian Science Publishing, 2021) Hobbs, James; Baxter, Randall; Lewis, Levi S.; Benjamin, Alyssa; Finger, Amanda J.; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Sağlam, İsmail Kudret; Faculty Member; College of Sciences; 168783The southernmost stock of longfin smelt (Spirinchus thaleichthys) is approaching extirpation in the San Francisco Estuary (SFE); however, patterns of genetic structure, diversity and gene flow which are vital for management are poorly understood in this species. Here, we use genome-wide data to evaluate population structure of longfin smelt across a broad latitudinal scale across estuaries ranging from the SFE to Yakutat Bay and Lake Washington, and fine scale within the Fraser River and the SFE. Results indicate high genetic structure between major estuaries, fine-scale structure within the Fraser River, and low levels of structure within the SFE. Genetic structure was more pronounced between northern estuaries whereas southern estuaries showed shared ancestry and ongoing gene flow, most notably unidirectional northward migration out of the SFE. Furthermore, we detected signatures of local adaptation within the Fraser River and the Skeena River estuaries. Taken together, our results identify broad patterns of genetic diversity in longfin smelt shaped by co-ancestry, unidirectional migration and local adaptation. Results also suggest that the SFE population is genetically distinct from northernmost populations and an important source for maintaining nearby populations.Publication Open Access Neural substrates of the drift-diffusion model in brain disorders(Frontiers, 2022) Gupta, A.; Bansal, R.; Alashwal, H.; Moustafa A.A.; Balcı, Fuat; Kaçar, Anıl Şafak; Faculty Member; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; 51269; N/AMany studies on the drift-diffusion model (DDM) explain decision-making based on a unified analysis of both accuracy and response times. This review provides an in-depth account of the recent advances in DDM research which ground different DDM parameters on several brain areas, including the cortex and basal ganglia. Furthermore, we discuss the changes in DDM parameters due to structural and functional impairments in several clinical disorders, including Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Obsessive-Compulsive Disorder (OCD), and schizophrenia. This review thus uses DDM to provide a theoretical understanding of different brain disorders.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; 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; 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.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; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; 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 Multi-modal communication: song sparrows increase signal redundancy in noise(The Royal Society, 2019) Beecher, Michael D.; Department of Psychology; Department of Psychology; Akçay, Çağlar; Faculty Member; College of Social Sciences and Humanities; 272053Although the effects of anthropogenic noise on animal communication have been studied widely, most research on the effect of noise in communication has focused on signals in a single modality. Consequently, how multi-modal communication is affected by anthropogenic noise is relatively poorly understood. Here, we ask whether song sparrows (Melospiza melodia) show evidence of plasticity in response to noise in two aggressive signals in acoustic and visual modalities. We test two hypotheses: (i) that song sparrows will shift signalling effort to the visual modality (the multi-modal shift hypothesis) and (ii) that they will increase redundancy of their multi-modal signalling (the back-up signal hypothesis). We presented male song sparrows with song playback and a taxidermic mount with or without a low-frequency acoustic noise from a nearby speaker. We found that males did not switch their signalling effort to visual modality (i.e. wing waves) in response to the noise. However, the correlation between warbled soft songs and wing waves increased in the noise treatment, i.e. signals became more redundant. These results suggest that when faced with anthropogenic noise, song sparrows can increase the redundancy of their multi-modal signals, which may aid in the robustness of the communication system.Publication Open Access Spatial and temporal variability in migration of a soaring raptor across three continents(Frontiers, 2019) Phipps, W. Louis; Lopez-Lopez, Pascual; Buechley, Evan R.; Oppel, Steffen; Alvarez, Ernesto; Arkumarev, Volen; Bekmansurov, Rinur; Berger-Tal, Oded; Bermejo, Ana; Bounas, Anastasios; Carbonell Alanis, Isidoro; de la Puente, Javier; Dobrev, Vladimir; Duriez, Olivier; Efrat, Ron; Frechet, Guillaume; Garcia, Javier; Galan, Manuel; Garcia-Ripolles, Clara; Gil, Alberto; Jose Iglesias-Lebrija, Juan; Jambas, Jose; Karyakin, Igor V.; Kobierzycki, Erick; Kret, Elzbieta; Loercher, Franziska; Monteiro, Antonio; Morant Etxebarria, Jon; Nikolov, Stoyan C.; Pereira, Jose; Peske, Lubomir; Ponchon, Cecile; Realinho, Eduardo; Saravia, Victoria; Skartsi, Theodora; Tavares, Jose; Teodosio, Joaquim; Urios, Vicente; Vallverdu, Nuria; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of SciencesDisentangling individual- and population-level variation in migratory movements is necessary for understanding migration at the species level. However, very few studies have analyzed these patterns across large portions of species' distributions. We compiled a large telemetry dataset on the globally endangered egyptian vulture neophron percnopterus (94 individuals, 188 completed migratory journeys), tracked across similar to 70% of the species' global range, to analyze spatial and temporal variability of migratory movements within and among individuals and populations. We found high migratory connectivity at large spatial scales (i.e., different subpopulations showed little overlap in wintering areas), but very diffuse migratory connectivity within subpopulations, with wintering ranges up to 4,000 km apart for birds breeding in the same region and each subpopulation visiting up to 28 countries (44 in total). Additionally, egyptian vultures exhibited a high level of variability at the subpopulation level and flexibility at the individual level in basic migration parameters. Subpopulations differed significantly in travel distance and straightness of migratory movements, while differences in migration speed and duration differed as much between seasons and among individuals within subpopulations as between subpopulations. The total distances of the migrations completed by individuals from the balkans and caucasus were up to twice as long and less direct than those in western europe, and consequently were longer in duration, despite faster migration speeds. These differences appear to be largely attributable to more numerous and wider geographic barriers (water bodies) along the eastern flyway. We also found that adult spring migrations to Western europe and the balkans were longer and slower than fall migrations. We encourage further research to assess the underlying mechanisms for these differences and the extent to which environmental change could affect egyptian vulture movement ecology and population trends.