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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 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 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 Omnivory in birds is a macroevolutionary sink(Nature Publishing Group (NPG), 2016) Burin, Gustavo; Kissling, W. Daniel; Guimaraes, Paulo R., Jr.; Quental, Tiago B.; N/A; Şekercioğlu, Çağan Hakkı; Faculty Member; College of SciencesDiet is commonly assumed to affect the evolution of species, but few studies have directly tested its effect at macroevolutionary scales. Here we use Bayesian models of trait-dependent diversification and a comprehensive dietary database of all birds worldwide to assess speciation and extinction dynamics of avian dietary guilds (carnivores, frugivores, granivores, herbivores, insectivores, nectarivores, omnivores and piscivores). Our results suggest that omnivory is associated with higher extinction rates and lower speciation rates than other guilds, and that overall net diversification is negat0ive. Trait-dependent models, dietary similarity and network analyses show that transitions into omnivory occur at higher rates than into any other guild. We suggest that omnivory acts as macroevolutionary sink, where its ephemeral nature is retrieved through transitions from other guilds rather than from omnivore speciation. We propose that these dynamics result from competition within and among dietary guilds, influenced by the deep-time availability and predictability of food resources.Publication Open Access In silico drug repositioning against human NRP1 to block SARS-CoV-2 host entry(TÜBİTAK, 2021) Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Gül, Şeref; Researcher; Graduate School of Sciences and EngineeringDespite COVID-19 turned into a pandemic, no approved drug for the treatment or globally available vaccine is out yet. In such a global emergency, drug repurposing approach that bypasses a costly and long-time demanding drug discovery process is an effective way in search of finding drugs for the COVID-19 treatment. Recent studies showed that SARS-CoV-2 uses neuropilin-1 (NRP1) for host entry. Here we took advantage of structural information of the NRP1 in complex with C-terminal of spike (S) protein of SARSCoV-2 to identify drugs that may inhibit NRP1 and S protein interaction. U.S. Food and Drug Administration (FDA) approved drugs were screened using docking simulations. Among top drugs, well-tolerated drugs were selected for further analysis. Molecular dynamics (MD) simulations of drugs-NRP1 complexes were run for 100 ns to assess the persistency of binding. MM/GBSA calculations from MD simulations showed that eltrombopag, glimepiride, sitagliptin, dutasteride, and ergotamine stably and strongly bind to NRP1. In silico Alanine scanning analysis revealed that Tyr(297), Trp(301), and Tyr(353) amino acids of NRP1 are critical for drug binding. Validating the effect of drugs analyzed in this paper by experimental studies and clinical trials will expedite the drug discovery process for COVID-19.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 Song overlapping, noise, and territorial aggression in great tits(Oxford University Press (OUP), 2020) Avşar, Alican; Bilgin, C. Can; Department of Psychology; Department of Psychology; Akçay, Çağlar; Porsuk, Yasin Kağan; Çabuk, Dilan; Faculty Member; Teaching Faculty; College of Social Sciences and Humanities; Graduate School of Social Sciences and Humanities; 272053; N/A; N/ACommunication often happens in noisy environments where interference from the ambient noise and other signalers may reduce the effectiveness of signals which may lead to more conflict between interacting individuals. Signalers may also evolve behaviors to interfere with signals of opponents, for example, by temporally overlapping them with their own, such as the song overlapping behavior that is seen in some songbirds during aggressive interactions. Song overlapping has been proposed to be a signal of aggressive intent, but few studies directly examined the association between song overlapping and aggressive behaviors of the sender. In the present paper, we examined whether song overlapping and ambient noise are associated positively with aggressive behaviors. We carried out simulated territorial intrusions in a population of great tits (Pares major) living in an urban-rural gradient to assess signaling and aggressive behaviors. Song overlapping was associated negatively with aggressive behaviors males displayed against a simulated intruder. This result is inconsistent with the hypothesis that song overlapping is an aggressive signal in this species. Ambient noise levels were associated positively with aggressive behaviors but did not correlate with song rate, song duration, or song overlapping. Great tits in noisy urban habitats may display higher levels of aggressive behaviors due to either interference of noise in aggressive communication or another indirect effect of noise.Publication Open Access Phylogeny, genetic diversity and population structure of Brandt's hedgehog Paraechinus hypomelas, inferred from the mitochondrial evidences(Arak University, 2019) Kashani, Ehsan; Rezaei, Hamid Reza; Khorasani, Nematolah; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Researcher; Graduate School of Sciences and EngineeringThe Brandt's hedgehog Paraechinus hypomelas (Brandt 1836), is a relatively widespread species which range from Arabian Peninsula and Iran, through southern areas of Central Asia to western South Asia. The phylogenetic position of the species tat is little known in Iran, although it has been studied in different parts of its distributional range. To this aim, during 2017-2018, the species was sampled in a non-invasive method (n=34) from the southeast of Iran. Genetic variation and polymorphic sites were determined from cytb (1120bp). Totally 22 haplotypes and haplotype diversity ranging from 0.859 to 1.099 were detected from cytb. The average value of the nucleotide differences among the cytb sequences was calculated as 4.68. The Tamija's D test (-1.88) and Fu's FS test (-15.73) revealed negative value, indicating significantly deviations from neutrality which both indicate of recent population expansion. Investigation on pairwise differences, mismatch distributions, indicated of past expansions (SSD= 0.0033, P value = 0.38). The Iran south east population constitute a phylogenetic clade which is completely distinct from other known lineages in the species distributional range. Relatively high amount of the haplotype and nucleotide diversity can be related to the high effective population of the species, the rate of gene flow among the populations and also the sudden expansion in the past.