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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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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 CLIC4 and CLIC1 bridge plasma membrane and cortical actin network for a successful cytokinesis(Life Science Alliance LLC, 2020) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Kagiali, Zeynep Cansu Üretmen; Şanal, Erdem; Değirmenci, Beste Senem; Mollaoğlu, Gürkan; Saner, Nazan; Master Student; Faculty Member; Researcher; 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; 227757CLIC4 and CLIC1 are members of the well-conserved chloride intracellular channel proteins (CLICs) structurally related to glutathione-S-transferases. Here, we report new roles of CLICs in cytokinesis. At the onset of cytokinesis, CLIC4 accumulates at the cleavage furrow and later localizes to the midbody in a RhoA-dependent manner. The cell cycle-dependent localization of CLIC4 is abolished when its glutathione S-transferase activity-related residues (C35A and F37D) are mutated. Ezrin, anillin, and ALIX are identified as interaction partners of CLIC4 at the cleavage furrow and midbody. Strikingly, CLIC4 facilitates the activation of ezrin at the cleavage furrow and reciprocally inhibition of ezrin activation diminishes the translocation of CLIC4 to the cleavage furrow. Furthermore, knockouts of CLIC4 and CLIC1 cause abnormal blebbing at the polar cortex and regression of the cleavage furrow at late cytokinesis leading to multinucleated cells. We conclude that CLIC4 and CLIC1 function together with ezrin where they bridge plasma membrane and actin cytoskeleton at the polar cortex and cleavage furrow to promote cortical stability and successful completion of cytokinesis in mammalian cells.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; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Faculty Member; 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 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.Publication Open Access Tapping into non-English-language science for the conservation of global biodiversity(Public Library of Science, 2021) Amano, Tatsuya; Berdejo-Espinola, Violeta; Christie, Alec P.; Willott, Kate; Akasaka, Munemitsu; Baldi, Andras; Berthinussen, Anna; Bertolino, Sandro; Bladon, Andrew J.; Chen, Min; Choi, Chang-Yong; Kharrat, Magda Bou Dagher; de Oliveira, Luis G.; Farhat, Perla; Golivets, Marina; Aranzamendi, Nataly Hidalgo; Jantke, Kerstin; Kajzer-Bonk, Joanna; Khorozyan, Igor; Kito, Kensuke; Konno, Ko; Lin, Da-Li; Littlewood, Nick; Liu, Yang; Liu, Yifan; Loretto, Matthias-Claudio; Marconi, Valentina; Martin, Philip A.; Morgan, William H.; Narvaez-Gomez, Juan P.; Negret, Pablo Jose; Nourani, Elham; Ochoa Quintero, Jose M.; Ockendon, Nancy; Oh, Rachel Rui Ying; Petrovan, Silviu O.; Piovezan-Borges, Ana C.; Pollet, Ingrid L.; Ramos, Danielle L.; Segovia, Ana L. Reboredo; Nayelli Rivera-Villanueva, A.; Rocha, Ricardo; Rouyer, Marie-Morgane; Sainsbury, Katherine; Schuster, Richard; Schwab, Dominik; Seo, Hae-Min; Shackelford, Gorm; Shinoda, Yushin; Smith, Rebecca K.; Tao, Shan-dar; Tsai, Ming-shan; Tyler, Elizabeth H. M.; Vajna, Flora; Valdebenito, Jose Osvaldo; Vozykova, Svetlana; Waryszak, Pawel; Zamora-Gutierrez, Veronica; Zenni, Rafael D.; Zhou, Wenjun; Sutherland, William J.; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Aytekin, M. Çisel Kemahlı; Faculty Member; College of Sciences; Graduate School of Sciences and Engineering; 327589; N/AThe widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2 degrees x 2 degrees grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges.Publication Open Access Human CRY1 variants associate with attention deficit/hyperactivity disorder(American Society for Clinical Investigation (ASCI), 2020) Onat, O. Emre; Kars, M. Ece; Bilguvar, Kaya; Wu, Yiming; Özhan, Ayşe; Trusso, M. Allegra; Goracci, Arianna; Fallerini, Chiara; Renieri, Alessandra; Casanova, Jean Laurent; Itan, Yuval; Atbaşoğlu, Cem E.; Saka, Meram C.; Özçelik, Tayfun; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Gül, Şeref; Aydın, Cihan; Başak, Ayşe Nazlı; Kavaklı, İbrahim Halil; Researcher; Researcher; 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 Engineering; College of Sciences; N/A; 214696; 1512; 40319Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as "circiatric" disorders.