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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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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 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 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 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 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 Cooperative allostery and structural dynamics of streptavidin at cryogenic- and ambient-temperature(Springer Nature, 2022) Yefanov, Oleksandr M.; Barty, Anton; Tolstikova, Alexandra; Ketawala, Gihan K.; Botha, Sabine; Dao, E. Han; Hayes, Brandon; Liang, Mengning; Seaberg, Matthew H.; Hunter, Mark S.; Batyuk, Alexander; Mariani, Valerio; Su, Zhen; Poitevin, Frederic; Yoon, Chun Hong; Kupitz, Christopher; Cohen, Aina; Doukov, Tzanko; Sierra, Raymond G.; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Dağ, Çağdaş; Ayan, Esra; Yüksel, Büşra; Destan, Ebru; Ertem, Fatma Betül; Yıldırım, Günseli; Eren, Meryem; Demirci, Hasan; Faculty Member; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 307350Ayan et al. report two structures of the protein streptavidin - one at ambient temperature determined using serial femtosecond crystallography and a second one determined at cryogenic temperature. These results provide insights into the structural dynamics of apo streptavidin and reveal a cooperative allostery between monomers for binding to biotin, and the findings are supported by GNM analysis. Multimeric protein assemblies are abundant in nature. Streptavidin is an attractive protein that provides a paradigm system to investigate the intra- and intermolecular interactions of multimeric protein complexes. Also, it offers a versatile tool for biotechnological applications. Here, we present two apo-streptavidin structures, the first one is an ambient temperature Serial Femtosecond X-ray crystal (Apo-SFX) structure at 1.7 angstrom resolution and the second one is a cryogenic crystal structure (Apo-Cryo) at 1.1 angstrom resolution. These structures are mostly in agreement with previous structural data. Combined with computational analysis, these structures provide invaluable information about structural dynamics of apo streptavidin. Collectively, these data further reveal a novel cooperative allostery of streptavidin which binds to substrate via water molecules that provide a polar interaction network and mimics the substrate biotin which displays one of the strongest affinities found in nature.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.Publication Open Access Proximity mapping of the microtubule plus-end tracking protein SLAIN2 using the BioID approach(TÜBİTAK, 2020) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Faculty Member; College of Sciences; 206349The centrosome is the main microtubule-organizing center of animal cells, which plays key roles in critical cellular processes ranging from cell division to cellular signaling. Accordingly, defects in the structure and function of centrosomes cause various human diseases such as cancer and primary microcephaly. To elucidate the molecular defects underlying these diseases, the biogenesis and functions of the centrosomes have to be fully understood. An essential step towards addressing these questions is the identification and functional dissection of the full repertoire of centrosome proteins. Here, we used high-resolution imaging and showed that the microtubule plus-end tracking protein SLAIN2 localizes to the pericentriolar material at the proximal end of centrioles. To gain insight into its cellular functions and mechanisms, we applied in vivo proximity-dependent biotin identification to SLAIN2 and generated its proximity interaction map. Gene ontology analysis of the SLAIN2 interactome revealed extensive interactions with centriole duplication, ciliogenesis, and microtubule-associated proteins, including previously characterized and uncharacterized interactions. Collectively, our results define SLAIN2 as a component of pericentriolar material and provide an important resource for future studies aimed at elucidating SLAIN2 functions at the centrosome.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.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.