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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; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; 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 Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication(Nature Portfolio, 2021) Yurtman, Erinç; Özer, Onur; Yüncü, Eren; Dağtaş, Nihan Dilşad; Koptekin, Dilek; Çakan, Yasin Gökhan; Özkan, Mustafa; Akbaba, Ali; Kaptan, Damla; Atağ, Gözde; Vural, Kıvılcım Başak; Gündem, Can Yümni; Martin, Louise; Kılınç, Gülşah Merve; Ghalichi, Ayshin; Açan, Sinan Can; Yaka, Reyhan; Sağlıcan, Ekin; Lagerholm, Vendela Kempe; Krzewinska, Maja; Gunther, Torsten; Miranda, Pedro Morell; Pişkin, Evangelia; Sevketoğlu, Müge; Bilgin, C. Can; Atakuman, Ciğdem; Erdal, Yılmaz Selim; Sürer, Elif; Altınışık, N. Ezgi; Lenstra, Johannes A.; Yorulmaz, Sevgi; Abazari, Mohammad Foad; Hoseinzadeh, Javad; Baird, Douglas; Bıcakcı, Erhan; Çevik, Özlem; Gerritsen, Fokke; Gotherstrom, Anders; Somel, Mehmet; Togan, İnci; Özer, Füsun; Department of Archeology and History of Art; Özbal, Rana; Faculty Member; Department of Archeology and History of Art; College of Social Sciences and Humanities; 55583Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.Publication Open Access Bacterial tail anchors can target to the mitochondrial outer membrane(BioMed Central, 2017) Department of Molecular Biology and Genetics; Lutfullahoglu-Bal, Guleycan; Keskin, Abdurrahman; Seferoğlu, Ayşe Bengisu; Dunn, Cory David; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesBackground: During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol. Results: Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM. Conclusions: Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.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; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; 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; Şekercioğlu, Çağan Hakkı; Aytekin, M. Çisel Kemahlı; Faculty Member; Department of Molecular Biology and Genetics; 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 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.
Publication Metadata only Time-based reward maximization(Royal Soc Chemistry, 2014) Zeki, Mustafa; N/A; Department of Psychology; Çavdaroğlu, Bilgehan; Balcı, Fuat; Master Student; Faculty Member; Department of Psychology; Graduate School of Social Sciences and Humanities; College of Social Sciences and Humanities; N/A; 51269Humans and animals time intervals from seconds to minutes with high accuracy but limited precision. Consequently, time-based decisions are inevitably subjected to our endogenous timing uncertainty, and thus require temporal risk assessment. In this study, we tested temporal risk assessment ability of humans when participants had to withhold each subsequent response for a minimum duration to earn reward and each response reset the trial time. Premature responses were not penalized in Experiment 1 but were penalized in Experiment 2. Participants tried to maximize reward within a fixed session time (over eight sessions) by pressing a key. No instructions were provided regarding the task rules/parameters. We evaluated empirical performance within the framework of optimality that was based on the level of endogenous timing uncertainty and the payoff structure. Participants nearly tracked the optimal target inter-response times (IRTs) that changed as a function of the level of timing uncertainty and maximized the reward rate in both experiments. Acquisition of optimal target IRT was rapid and abrupt without any further improvement or worsening. These results constitute an example of optimal temporal risk assessment performance in a task that required finding the optimal trade-off between the 'speed' (timing) and 'accuracy' (reward probability) of timed responses for reward maximization.