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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; Sağlam, İsmail Kudret; Faculty Member; Department of Molecular Biology and Genetics; 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 ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium content regulation(Wiley, 2022) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Tiryaki, Fatmanur; Deretic, Jovana; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 206349Centrioles and cilia are conserved, microtubule-based structures critical for cell function and development. Their dysfunction causes cancer and developmental disorders. How microtubules are organized into ordered structures by microtubule-associated proteins (MAPs) and tubulin modifications is best understood during mitosis but is largely unexplored for the centrioles and the ciliary axoneme, which are composed of stable microtubules that maintain their length at a steady-state. In particular, we know little about the identity of the centriolar and ciliary MAPs and how they work together during the assembly and maintenance of the cilium and centriole. Here, we identified the Enkurin domain containing 1 (ENKD1) as a component of the centriole wall and the axoneme in mammalian cells and showed that it has extensive proximity interactions with these compartments and MAPs. Using in vitro and cellular assays, we found that ENKD1 is a new MAP that regulates microtubule organization and stability. Consistently, we observed an increase in tubulin polymerization and microtubule stability, as well as disrupted microtubule organization in ENKD1 overexpression. Cells depleted for ENKD1 were defective in ciliary length and content regulation and failed to respond to Hedgehog pathway activation. Together, our results advance our understanding of the functional and regulatory relationship between MAPs and the primary cilium.Publication Open Access A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells(Nature Publishing Group (NPG), 2018) Seferoğlu, Ayşe Bengisu; Department of Molecular Biology and Genetics; Dunn, Cory David; Keskin, Abdurrahman; Akdoğan, Emel; Lutfullahoglu-Bal, Guleycan; Department of Molecular Biology and Genetics; College of SciencesProkaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential in the era of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous, peroxisome-directed TA. Furthermore, the YgiM(TA) can localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool allowing further illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.Publication Open Access Single transverse mode protein laser(American Institute of Physics (AIP) Publishing, 2017) Min, Kyungtaek; Kim, Sunghwan; Umar, Muhammad; Department of Molecular Biology and Genetics; Department of Electrical and Electronics Engineering; Doğru-Yüksel, Itır Bakış; Jalali, Houman Bahmani; Begar, Efe; Çonkar, Deniz; Karalar, Elif Nur Fırat; Nizamoğlu, Sedat; PhD Student; PhD Student; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Electrical and Electronics Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; N/A; N/A; N/A; 130295Here, we report a single transverse mode distributed feedback (DFB) protein laser. The gain medium that is composed of enhanced green fluorescent protein in a silk fibroin matrix yields a waveguiding gain layer on a DFB resonator. The thin TiO2 layer on the quartz grating improves optical feedback due to the increased effective refractive index. The protein laser shows a single transverse mode lasing at the wavelength of 520 nm with the threshold level of 92.1 mu J/mm(2).Publication Open Access Combining models of environment, behavior, and physiology to predict tissue hydrogen and oxygen isotope variance among individual terrestrial animals(Frontiers, 2020) Magozzi, Sarah; Vander Zanden, Hannah B.; Wunder, Michael B.; Trueman, Clive N.; Pinney, Kailee; Peers, Dori; Dennison, Philip E.; Horns, Joshua J.; Bowen, Gabriel J.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of SciencesVariations in stable hydrogen and oxygen isotope ratios in terrestrial animal tissues are used to reconstruct origin and movement. An underlying assumption of these applications is that tissues grown at the same site share a similar isotopic signal, representative of the location of their origin. However, large variations in tissue isotopic compositions often exist even among conspecific individuals within local populations, which complicates origin and migration inferences. Field-data and correlation analyses have provided hints about the underlying mechanisms of within-site among-individual isotopic variance, but a theory explaining the causes and magnitude of such variance has not been established. Here we develop a mechanistic modeling framework that provides explicit predictions of the magnitude, patterns, and drivers of isotopic variation among individuals living in a common but environmentally heterogeneous habitat. The model toolbox includes isoscape models of environmental isotopic variability, an agent-based model of behavior and movement, and a physiology-biochemistry model of isotopic incorporation into tissues. We compare model predictions against observed variation in hatch-year individuals of the songbird Spotted Towhee (Pipilo maculatus) in Red Butte Canyon, Utah, and evaluate the ability of the model to reproduce this variation under different sets of assumptions. Only models that account for environmental isotopic variability predict a similar magnitude of isotopic variation as observed. Within the modeling framework, behavioral rules and properties govern how animals nesting in different locations acquire resources from different habitats, and birds nesting in or near riparian habitat preferentially access isotopically lighter resources than those associated with the meadow and slope habitats, which results in more negative body water and tissue isotope values. Riparian nesters also have faster body water turnover and acquire more water from drinking (vs. from food), which exerts a secondary influence on their isotope ratios. Thus, the model predicts that local among-individual isotopic variance is linked first to isotopic heterogeneity in the local habitat, and second to how animals sample this habitat during foraging. Model predictions provide insight into the fundamental mechanisms of small-scale isotopic variance and can be used to predict the utility of isotope-based methods for specific groups or environments in ecological and forensic research.Publication Open Access In vitro cytotoxicity evaluation of plastoquinone analogues against colorectal and breast cancers along with in silico insights(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Sever, B.; Bayrak, N.; Yıldız, M.; Yıldırım, H.; Tateishi, H.; Otsuka, M.; Fujita M.; Tuyun, A.F.; Department of Molecular Biology and Genetics; Çiftçi, Halil İbrahim; Researcher; Department of Molecular Biology and Genetics; College of SciencesColorectal cancer (CRC) and breast cancer are leading causes of death globally, due to significant challenges in detection and management. The late-stage diagnosis and treatment failures require the discovery of potential anticancer agents to achieve a satisfactory therapeutic effect. We have previously reported a series of plastoquinone analogues to understand their cytotoxic profile. Among these derivatives, three of them (AQ-11, AQ-12, and AQ-15) were selected by the National Cancer Institute (NCI) to evaluate their in vitro antiproliferative activity against a panel of 60 human tumor cell lines. AQ-12 exhibited significant antiproliferative activity against HCT-116 CRC and MCF-7 breast cancer cells at a single dose and further five doses. MTT assay was also performed for AQ-12 at different concentrations against these two cells, implying that AQ-12 exerted notable cytotoxicity toward HCT-116 (IC50 = 5.11 ± 2.14 ?M) and MCF-7 (IC50 = 6.06 ± 3.09 ?M) cells in comparison with cisplatin (IC50 = 23.68 ± 6.81 ?M and 19.67 ± 5.94 ?M, respectively). This compound also augmented apoptosis in HCT-116 (62.30%) and MCF-7 (64.60%) cells comparable to cisplatin (67.30% and 78.80%, respectively). Molecular docking studies showed that AQ-12 bound to DNA, forming hydrogen bonding through the quinone scaffold. In silico pharmacokinetic determinants indicated that AQ-12 demonstrated drug-likeness with a remarkable pharmacokinetic profile for future mechanistic anti-CRC and anti-breast cancer activity studies.Publication Open Access Low-signal limit of X-ray single particle diffractive imaging(Optical Society of America (OSA), 2019) Ayyer, Kartik; Morgan, Andrew J.; Aquila, Andrew; Hogue, Brenda G.; Kirian, Richard A.; Xavier, P. Lourdu; Yoon, Chun Hong; Chapman, Henry N.; Barty, Anton; Department of Molecular Biology and Genetics; Demirci, Hasan; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 307350An outstanding question in X-ray single particle imaging experiments has been the feasibility of imaging sub 10-nm-sized biomolecules under realistic experimental conditions where very few photons are expected to be measured in a single snapshot and instrument background may be significant relative to particle scattering. While analyses of simulated data have shown that the determination of an average image should be feasible using Bayesian methods such as the EMC algorithm, this has yet to be demonstrated using experimental data containing realistic non-isotropic instrument background, sample variability and other experimental factors. In this work, we show that the orientation and phase retrieval steps work at photon counts diluted to the signal levels one expects from smaller molecules or with weaker pulses, using data from experimental measurements of 60-nm PR772 viruses. Even when the signal is reduced to a fraction as little as 1/256, the virus electron density determined using ab initio phasing is of almost the same quality as the high-signal data. However, we are still limited by the total number of patterns collected, which may soon be mitigated by the advent of high repetition-rate sources like the European XFEL and LCLS-II.Publication Open Access Hares, humans, and lynx activity rhythms: who avoids whom?(Associazione Teriologica Italiana, 2021) Kuşak, J.; Bojarska, K.; Chynoweth, M.; Green, A.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Naderi, Mortaza; Faculty Member; Researcher; Department of Molecular Biology and Genetics; College of Sciences; 327589; N/APredator-prey interactions and human presence are among the key factors shaping large mammal activity patterns. In human-dominated landscapes, large carnivores must balance their activity rhythms between optimizing feeding opportunities and avoiding encounters with humans. In northeastern Turkey, the Caucasian lynx (Lynx lynx dinniki), a threatened subspecies of the Eurasian lynx (Lynx lynx), occupies habitats that are heavily fragmented and dominated by human presence in the warm part of the year. Using camera traps and GPS-collar activity sensors, we investigated lynx circadian activity patterns across lunar phases and seasons. We compared the activity pattern of the lynx to the activity pattern of its primary prey, the European hare (Lepus europaeus), and humans. We found that during the warm season (May-October), lynx displayed a bimodal crepuscular activity pattern typical for this species and consistent with hare activity. During the cold season (November-April), both lynx and hares shifted to predominantly diurnal activity. During the full moon, hares reduced their activity due to the anti-predator behaviour, followed by a corresponding adjustment in lynx activity patterns. We conclude that lynx activity in our study area is an outcome of weather conditions, human presence and foraging behaviour. Our results also corroborate the suitability of camera trapping data in documenting multiple species' temporal activity patterns.Publication Open Access Metabolic reprogramming in adipose tissue during cancer cachexia(Frontiers, 2022) Department of Molecular Biology and Genetics; Weber, Bahar Zehra Camurdanoğlu; Arabacı, Hilal Dilşad; Kır, Serkan; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 274185Cancer cachexia is a disorder of energy balance characterized by the wasting of adipose tissue and skeletal muscle resulting in severe weight loss with profound influence on morbidity and mortality. Treatment options for cancer cachexia are still limited. This multifactorial syndrome is associated with changes in several metabolic pathways in adipose tissue which is affected early in the course of cachexia. Adipose depots are involved in energy storage and consumption as well as endocrine functions. In this mini review, we discuss the metabolic reprogramming in all three types of adipose tissues - white, brown, and beige - under the influence of the tumor macro-environment. Alterations in adipose tissue lipolysis, lipogenesis, inflammation and adaptive thermogenesis of beige/brown adipocytes are highlighted. Energy-wasting circuits in adipose tissue impacts whole-body metabolism and particularly skeletal muscle. Targeting of key molecular players involved in the metabolic reprogramming may aid in the development of new treatment strategies for cancer cachexia.Publication Open Access The secondary pocket of cryptochrome 2 is important for the regulation of its stability and localization(Elsevier, 2022) Gül, Şeref; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Kavaklı, İbrahim Halil; Barış, İbrahim; Özcan, Onur; Faculty Member; Teaching Faculty; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 40319; 111629; N/A; N/A; N/AHuman clock-gene variations contribute to the phenotypic differences observed in various behavioral and physiological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. However, little is known about the possible effects of identified variations at the molecular level. In this study, we performed a functional characterization at the cellular level of rare cryptochrome 2 (CRY2) missense variations that were identified from the Ensembl database. Our structural studies revealed that three variations (p.Pro123Leu, p.Asp406His, and p.Ser410Ile) are located at the rim of the secondary pocket of CRY2. We show that these variants were unable to repress CLOCK (circadian locomotor output cycles kaput)/BMAL1 (brain and muscle ARNT-like-1)-driven transcription in a cell-based reporter assay and had reduced affinity to CLOCK-BMAL1. Furthermore, our biochemical studies indicated that the variants were less stable than the WT CRY2, which could be rescued in the presence of period 2 (PER2), another core clock protein. Finally, we found that these variants were unable to properly localize to the nucleus and thereby were unable to rescue the circadian rhythm in a Cry1(-/-)Cry2(-/-) double KO mouse embryonic fibroblast cell line. Collectively, our data suggest that the rim of the secondary pocket of CRY2 plays a significant role in its nuclear localization independently of PER2 and in the intact circadian rhythm at the cellular level.