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Journal articles on the topic 'Biogenetic resources'
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1
Riley, Mary. "Intellectual Property, Biogenetic Resources and Traditional Knowledge." Economic Botany 59, no. 3 (June 2005): 308. http://dx.doi.org/10.1663/0013-0001(2005)059[0308:dfabre]2.0.co;2.
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Jiang, Zhigang. "Meta-property right, derived property right and right of modification of biogenetic resources." Biodiversity Science 13, no. 4 (2005): 363. http://dx.doi.org/10.1360/biodiv.050084.
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Suranova, T. G., S. S. Zenin, and G. N. Suvorov. "PRINCIPLES AND PATTERNS OF LEGAL REGULATION OF GENOME-WIDE SEQUENCING IN THE PEOPLE’S REPUBLIC OF CHINA (PRC)." Issues of Law 20, no. 3 (2020): 81–86. http://dx.doi.org/10.14529/pro-prava200311.
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The global genome sequencing market is developing at a very fast pace, and this is happening most rapidly in China. Amid the economic boom, demand for advanced medical services is extremely high. In view of this, the principles and laws of normative regulation of this activity carried out using both legislative and administrative legal instruments deserve attention. For the domestic legislator, the Chinese experience in regulating the use of genetic resources in conducting international joint research, collecting, storing, using and providing external human genetic resources in China, and ethical principles in conducting biogenetic studies will be extremely useful.
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Tonye, Marcelin M. "Sui Generis Systems for the Legal Protection of Traditional Knowledge and Biogenetic Resources in Cameroon and South Africa." Journal of World Intellectual Property 6, no. 5 (November 1, 2005): 763–74. http://dx.doi.org/10.1111/j.1747-1796.2003.tb00241.x.
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Safriel, Uriel N., Sergei Volis, and Salit Kark. "CORE AND PERIPHERAL POPULATIONS AND GLOBAL CLIMATE CHANGE." Israel Journal of Plant Sciences 42, no. 4 (May 13, 1994): 331–45. http://dx.doi.org/10.1080/07929978.1994.10676584.
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Environmental conditions outside the periphery of a species' distribution prevent population persistence, hence peripheral populations live under conditions different from those of core populations. Peripheral areas are characterized by variable and unstable conditions, relative to core areas. Peripheral populations are expected to be genetically more variable, since the variable conditions induce fluctuating selection, which maintains high genetic diversity. Alternatively, due to marginal ecological conditions at the periphery, populations there are small and isolated; the within-population diversity is low, but the between-population genetic diversity is high due to genetic drift. It is also likely that peripheral populations evolve resistance to extreme conditions. Thus, peripheral populations rather than core ones may be resistant to environmental extremes and changes, such as global climate change induced by the anthropogenically emitted “greenhouse gases”. They should be treated as a biogenetic resource used for rehabilitation and restoration of damaged ecosystems. Climatic transition zones are characterized by a high incidence of species represented by peripheral populations, and therefore should be conserved now as repositories of these resources, to be used in the future for mitigating undesirable effects of global climate change. Preliminary research revealed high phenotypic variability and high genetic diversity in peripheral populations relative to core populations of wild barley and the chukar partridge, respectively.
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Pop, Alexandru-Leonard, and Mirela Coman. "IMPLICATIONS OF PHILATELY IN PROMOTING THE PROTECTED NATURAL AREAS (I): CEAHLĂU NATIONAL PARK." Scientific Bulletin Series D : Mining, Mineral Processing, Non-Ferrous Metallurgy, Geology and Environmental Engineering 32, no. 1 (2018): 87–96. http://dx.doi.org/10.37193/sbsd.2018.1.12.
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We define and accept natural heritage as being the ensemble of components and physical-geographic structures, flora, fauna and biocenotic natural resources, of whose importance has an ecological, economical, scientific, biogenetic, and health values, a recreative and cultural-historicvision iss having relevant significance under the aspect of conserving the biodiversity of ecosystems' functional integrity, genetical heritage conservation, vegetation and animals, and for the satisfaction of the everyday life , as well as wealth, culture and civilisation, of bothpresent and future generations. Romania is a blessed place with many areas of unique beauty - as part of the natural heritage - with places where the spectacle of nature delights your eyes and take your breath with every step. Constantly promoting philately themes that use natural wealth and the beauty of our country as subjects, the administrative entity (with various names over time) responsible for issuing postage stamps performs a series of postage stamps in whose images are found rarities of flora and fauna, a miracle of nature. In this paper, we bring to discussion, among other things, the most significant philatelic peculiarities in the Ceahlău National Park.
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Pop, Alexandru-Leonard, Yaroslav Adamenko, and Bogdan Cioruţa. "IMPLICATIONS OF PHILATELY IN PROMOTING THE PROTECTED NATURAL AREAS (II): "PE.EA CREEK" NATURAL RESERVATION." Scientific Bulletin Series D : Mining, Mineral Processing, Non-Ferrous Metallurgy, Geology and Environmental Engineering 32, no. 2 (2018): 43–52. http://dx.doi.org/10.37193/sbsd.2018.2.05.
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We define and accept natural heritage as being the ensemble of components and physical-geographical structures, floristic, faunistic and biocenotic of natural resources, of which importance and ecological value, economical, scientific, biogenetic, health, views, recreative and cultural-historic have relevant significance under the aspect of conserving biodiversity, of ecosystems functional integrity, genetical heritage conservation, vegetal and animal, and for life need satisfaction, wealth, culture and civilisation of present and future generations. Romania is a blessed place with many areas of unique beauty - as part of the natural heritage - with places where the spectacle of nature delights your eyes and breathtaking your every step. Constantly promoting philately themes that use natural wealth and beauty of our country as subjects, the administrative entity (with various names over time) responsible for issuing postage stamps performs a series of postage stamps in whose images are found rarities of flora and fauna, a miracle of nature. In this paper, we bring to discussion, among other things, the most significant philatelic peculiarities in the "Petea Creek " Natural Reservation.
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Safitri, Oktavia, Evi Suryawati, and Darmadi Darmadi. "PENGEMBANGAN VIDEO PERANCANGAN DAN PELAKSANAAN PRAKTIKUM BIOLOGI." Biogenesis 17, no. 1 (February 24, 2021): 19. http://dx.doi.org/10.31258/biogenesis.17.1.19-25.
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Regulation of the Minister of National Education of the Republic of Indonesia Number 16 of 2007 concerning Academic Qualification Standards and Teacher Competencies states that one of the competencies of high school biology teachers is the competence to properly design and implement practicum. Biology Education students as prospective biology teachers must master these competencies. The existence of independent learning resources can be used as a reference for prospective student teachers in studying material related to practicum activities. This study aims to produce independent learning resources in the form of videos. This research was conducted at the PMIPA Laboratory FKIP Riau University, SMAN 8 Pekanbaru and SMAN 15 Pekanbaru in April-December 2020. The type of research used was Research and Development (R&D) with the ADDIE model. The instruments used in this study were the validation sheet and response questionnaire. The results of the video validation obtained an average value of 3.57 with a very valid category. The results of the limited trial phase I obtained an average value of 3.64 in the very good category, while the results of the phase II trial obtained an average value of 3.43 in the very good category. Based on the results of the validation and trials, it shows that the video of the design and implementation of the biology practicum developed can be used as an independent learning resource for prospective biology teachers.
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Valisa, Viola Vinca, Evi Suryawati, and Arnentis Arnentis. "BUKU PENUNTUN PRAKTIKUM JARINGAN HEWAN MENGGUNAKAN VIRTUAL LABORATORY." Biogenesis 17, no. 2 (August 23, 2021): 81. http://dx.doi.org/10.31258/biogenesis.17.2.81-87.
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The most problem occurs in the praticum in the real laboratory, so it's not going well. It can affect the depth of concepts, principles, laws and theories that must be understood by the biology teacher candidates. One of the alternatives that can be done is practicum to use a virtual laboratory. The purpose of research is to develop a practical guidebook for animal tissue materials in practicum activities using virtual laboratories for teacher candidates. This research was conducted at the Laboratory of PMIPA FKIP Riau University in December 2020–May 2021. It used a Research and Development (R&D) approach with ADDIE model. The instruments used are validation expert and response questionnaires. The results showed that the guide books is good quality and suitable to be used as independent learning resources to increase content knowledge for teacher candidates.
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Kofler, Lisa, Michael Prattes, and Helmut Bergler. "From Snapshots to Flipbook—Resolving the Dynamics of Ribosome Biogenesis with Chemical Probes." International Journal of Molecular Sciences 21, no. 8 (April 23, 2020): 2998. http://dx.doi.org/10.3390/ijms21082998.
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The synthesis of ribosomes is one of the central and most resource demanding processes in each living cell. As ribosome biogenesis is tightly linked with the regulation of the cell cycle, perturbation of ribosome formation can trigger severe diseases, including cancer. Eukaryotic ribosome biogenesis starts in the nucleolus with pre-rRNA transcription and the initial assembly steps, continues in the nucleoplasm and is finished in the cytoplasm. From start to end, this process is highly dynamic and finished within few minutes. Despite the tremendous progress made during the last decade, the coordination of the individual maturation steps is hard to unravel by a conventional methodology. In recent years small molecular compounds were identified that specifically block either rDNA transcription or distinct steps within the maturation pathway. As these inhibitors diffuse into the cell rapidly and block their target proteins within seconds, they represent excellent tools to investigate ribosome biogenesis. Here we review how the inhibitors affect ribosome biogenesis and discuss how these effects can be interpreted by taking the complex self-regulatory mechanisms of the pathway into account. With this we want to highlight the potential of low molecular weight inhibitors to approach the dynamic nature of the ribosome biogenesis pathway.
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Charron, Audra J., and L. David Sibley. "Host cells: mobilizable lipid resources for the intracellular parasite Toxoplasma gondii." Journal of Cell Science 115, no. 15 (August 1, 2002): 3049–59. http://dx.doi.org/10.1242/jcs.115.15.3049.
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Successful replication of the intracellular parasite Toxoplasma gondii within its parasitophorous vacuole necessitates a substantial increase in membrane mass. The possible diversion and metabolism of host cell lipids and lipid precursors by Toxoplasma was therefore investigated using radioisotopic and fluorophore-conjugated compounds. Confocal microscopic analyses demonstrated that Toxoplasma is selective with regards to both the acquisition and compartmentalization of host cell lipids. Lipids were compartmentalized into parasite endomembranes and, in some cases, were apparently integrated into the surrounding vacuolar membrane. Additionally,some labels became concentrated in discrete lipid bodies that were biochemically and morphologically distinct from the parasite apical secretory organelles. Thin layer chromatography established that parasites readily scavenged long-chain fatty acids as well as cholesterol, and in certain cases modified the host-derived lipids. When provided with radiolabeled phospholipid precursors, including polar head groups, phosphatidic acid and small fatty acids, intracellular parasites preferentially accrued phosphatidylcholine(PtdCho) over other phospholipids. Moreover, Toxoplasma was found to be competent to synthesize PtdCho from radiolabeled precursors obtained from its environment. Together, these studies underscore the ability of Toxoplasma gondii to divert and use lipid resources from its host, a process that may contribute to the biogenesis of parasite membranes.
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Kim, Young-Kook, Boseon Kim, and V. Narry Kim. "Re-evaluation of the roles of DROSHA, Exportin 5, and DICER in microRNA biogenesis." Proceedings of the National Academy of Sciences 113, no. 13 (March 14, 2016): E1881—E1889. http://dx.doi.org/10.1073/pnas.1602532113.
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Biogenesis of canonical microRNAs (miRNAs) involves multiple steps: nuclear processing of primary miRNA (pri-miRNA) by DROSHA, nuclear export of precursor miRNA (pre-miRNA) by Exportin 5 (XPO5), and cytoplasmic processing of pre-miRNA by DICER. To gain a deeper understanding of the contribution of each of these maturation steps, we deleted DROSHA, XPO5, and DICER in the same human cell line, and analyzed their effects on miRNA biogenesis. Canonical miRNA production was completely abolished in DROSHA-deleted cells, whereas we detected a few DROSHA-independent miRNAs including three previously unidentified noncanonical miRNAs (miR-7706, miR-3615, and miR-1254). In contrast to DROSHA knockout, many canonical miRNAs were still detected without DICER albeit at markedly reduced levels. In the absence of DICER, pre-miRNAs are loaded directly onto AGO and trimmed at the 3′ end, yielding miRNAs from the 5′ strand (5p miRNAs). Interestingly, in XPO5 knockout cells, most miRNAs are affected only modestly, suggesting that XPO5 is necessary but not critical for miRNA maturation. Our study demonstrates an essential role of DROSHA and an important contribution of DICER in the canonical miRNA pathway, and reveals that the function of XPO5 can be complemented by alternative mechanisms. Thus, this study allows us to understand differential contributions of key biogenesis factors, and provides with valuable resources for miRNA research.
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Heikkinen, Hannu I. "Biogenetic Paradoxes of the Nation: Finncattle, Apples, and Other Genetic‐Resource Puzzles by SakariTamminen Durham, NC: Duke University Press, 2019. 272 pp." American Anthropologist 123, no. 2 (February 24, 2021): 443–44. http://dx.doi.org/10.1111/aman.13545.
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Whitney, Spencer M., Rosemary Birch, Celine Kelso, Jennifer L. Beck, and Maxim V. Kapralov. "Improving recombinant Rubisco biogenesis, plant photosynthesis and growth by coexpressing its ancillary RAF1 chaperone." Proceedings of the National Academy of Sciences 112, no. 11 (March 2, 2015): 3564–69. http://dx.doi.org/10.1073/pnas.1420536112.
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Enabling improvements to crop yield and resource use by enhancing the catalysis of the photosynthetic CO2-fixing enzyme Rubisco has been a longstanding challenge. Efforts toward realization of this goal have been greatly assisted by advances in understanding the complexities of Rubisco’s biogenesis in plastids and the development of tailored chloroplast transformation tools. Here we generate transplastomic tobacco genotypes expressing Arabidopsis Rubisco large subunits (AtL), both on their own (producing tobAtL plants) and with a cognate Rubisco accumulation factor 1 (AtRAF1) chaperone (producing tobAtL-R1 plants) that has undergone parallel functional coevolution with AtL. We show AtRAF1 assembles as a dimer and is produced in tobAtL-R1 and Arabidopsis leaves at 10–15 nmol AtRAF1 monomers per square meter. Consistent with a postchaperonin large (L)-subunit assembly role, the AtRAF1 facilitated two to threefold improvements in the amount and biogenesis rate of hybrid L8AS8t Rubisco [comprising AtL and tobacco small (S) subunits] in tobAtL-R1 leaves compared with tobAtL, despite >threefold lower steady-state Rubisco mRNA levels in tobAtL-R1. Accompanying twofold increases in photosynthetic CO2-assimilation rate and plant growth were measured for tobAtL-R1 lines. These findings highlight the importance of ancillary protein complementarity during Rubisco biogenesis in plastids, the possible constraints this has imposed on Rubisco adaptive evolution, and the likely need for such interaction specificity to be considered when optimizing recombinant Rubisco bioengineering in plants.
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Gomez, Rodrigo Enrique, Josselin Lupette, Clément Chambaud, Julie Castets, Amélie Ducloy, Jean-Luc Cacas, Céline Masclaux-Daubresse, and Amélie Bernard. "How Lipids Contribute to Autophagosome Biogenesis, a Critical Process in Plant Responses to Stresses." Cells 10, no. 6 (May 21, 2021): 1272. http://dx.doi.org/10.3390/cells10061272.
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Throughout their life cycle, plants face a tremendous number of environmental and developmental stresses. To respond to these different constraints, they have developed a set of refined intracellular systems including autophagy. This pathway, highly conserved among eukaryotes, is induced by a wide range of biotic and abiotic stresses upon which it mediates the degradation and recycling of cytoplasmic material. Central to autophagy is the formation of highly specialized double membrane vesicles called autophagosomes which select, engulf, and traffic cargo to the lytic vacuole for degradation. The biogenesis of these structures requires a series of membrane remodeling events during which both the quantity and quality of lipids are critical to sustain autophagy activity. This review highlights our knowledge, and raises current questions, regarding the mechanism of autophagy, and its induction and regulation upon environmental stresses with a particular focus on the fundamental contribution of lipids. How autophagy regulates metabolism and the recycling of resources, including lipids, to promote plant acclimation and resistance to stresses is further discussed.
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LEUNG, Anthony K. L., Jens S. ANDERSEN, Matthias MANN, and Angus I. LAMOND. "Bioinformatic analysis of the nucleolus." Biochemical Journal 376, no. 3 (December 15, 2003): 553–69. http://dx.doi.org/10.1042/bj20031169.
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The nucleolus is a plurifunctional, nuclear organelle, which is responsible for ribosome biogenesis and many other functions in eukaryotes, including RNA processing, viral replication and tumour suppression. Our knowledge of the human nucleolar proteome has been expanded dramatically by the two recent MS studies on isolated nucleoli from HeLa cells [Andersen, Lyon, Fox, Leung, Lam, Steen, Mann and Lamond (2002) Curr. Biol. 12, 1–11; Scherl, Coute, Deon, Calle, Kindbeiter, Sanchez, Greco, Hochstrasser and Diaz (2002) Mol. Biol. Cell 13, 4100–4109]. Nearly 400 proteins were identified within the nucleolar proteome so far in humans. Approx. 12% of the identified proteins were previously shown to be nucleolar in human cells and, as expected, nearly all of the known housekeeping proteins required for ribosome biogenesis were identified in these analyses. Surprisingly, approx. 30% represented either novel or uncharacterized proteins. This review focuses on how to apply the derived knowledge of this newly recognized nucleolar proteome, such as their amino acid/peptide composition and their homologies across species, to explore the function and dynamics of the nucleolus, and suggests ways to identify, in silico, possible functions of the novel/uncharacterized proteins and potential interaction networks within the human nucleolus, or between the nucleolus and other nuclear organelles, by drawing resources from the public domain.
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Nepal, Suruchi, Sandra Maaß, Stefano Grasso, Francis M. Cavallo, Jürgen Bartel, Dörte Becher, Erik Bathoorn, and Jan Maarten van Dijl. "Proteomic Charting of Imipenem Adaptive Responses in a Highly Carbapenem Resistant Clinical Enterobacter roggenkampii Isolate." Antibiotics 10, no. 5 (April 28, 2021): 501. http://dx.doi.org/10.3390/antibiotics10050501.
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Gram-negative bacteria belonging to the Enterobacter cloacae complex are increasingly implicated in difficult-to-treat nosocomial infections, as exemplified by a recently characterized highly carbapenem-resistant clinical Enterobacter roggenkampii isolate with sequence type (ST) 232. While mechanisms of carbapenem resistance are well-understood, little is known about the responses of highly drug-resistant bacteria to these antibiotics. Our present study was therefore aimed at charting the responses of the E. roggenkampii ST232 isolate to the carbapenem imipenem, using a ‘stable isotope labeling of amino acids in cell culture’ approach for quantitative mass spectrometry. This unveiled diverse responses of E. roggenkampii ST232 to imipenem, especially altered levels of proteins for cell wall biogenesis, central carbon metabolism, respiration, iron–sulfur cluster synthesis, and metal homeostasis. These observations suggest a scenario where imipenem-challenged bacteria reduce metabolic activity to save resources otherwise used for cell wall biogenesis, and to limit formation of detrimental reactive oxygen species at the cytoplasmic membrane due to respiration and Fenton chemistry. We consider these observations important, because knowing the adaptive responses of a highly resistant bacterium of the E. cloacae complex to last-resort antibiotics, such as imipenem, provides a ‘sneak preview’ into the future development of antibiotic resistance in this emerging group of pathogens.
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Iarovaia, Olga V., Elena S. Ioudinkova, Artem K. Velichko, and Sergey V. Razin. "Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals." Cells 10, no. 7 (June 25, 2021): 1597. http://dx.doi.org/10.3390/cells10071597.
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Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.
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Lin, Pei-Hsuan, Li-Te Lin, Chia-Jung Li, Pei-Gang Kao, Hsiao-Wen Tsai, San-Nung Chen, Zhi-Hong Wen, Peng-Hui Wang, and Kuan-Hao Tsui. "Combining Bioinformatics and Experiments to Identify CREB1 as a Key Regulator in Senescent Granulosa Cells." Diagnostics 10, no. 5 (May 11, 2020): 295. http://dx.doi.org/10.3390/diagnostics10050295.
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Aging of functional ovaries occurs many years before aging of other organs in the female body. In recent years, a greater number of women continue to postpone their pregnancies to later stages in their lives, raising concerns of the effect of ovarian aging. Mitochondria play an important role in the connection between the aging granulosa cells and oocytes. However, the underlying mechanisms of mitochondrial dysfunction in these cells remain poorly understood. Therefore, we evaluated the molecular mechanism of the aging granulosa cells, including aspects such as accumulation of mitochondrial reactive oxygen species, reduction of mtDNA, imbalance of mitochondrial dynamics, and diminished cell proliferation. Here, we applied bioinformatics approaches, and integrated publicly available resources, to investigate the role of CREB1 gene expression in reproduction. Senescence hallmark enrichment and pathway analysis suggested that the downregulation of bioenergetic-related genes in CREB1. Gene expression analyses showed alterations in genes related to energy metabolism and ROS production in ovary tissue. We also demonstrate that the biogenesis of aging granulosa cells is subject to CREB1 binding to the PRKAA1 and PRKAA2 upstream promoters. In addition, cofactors that regulate biogenesis significantly increase the levels of SIRT1 and PPARGC1A mRNA in the aging granulosa cells. These findings demonstrate that CREB1 elevates an oxidative stress-induced senescence in granulosa cells by reducing the mitochondrial function.
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Zimmermann, Céline, Isabelle Stévant, Christelle Borel, Béatrice Conne, Jean-Luc Pitetti, Pierre Calvel, Henrik Kaessmann, Bernard Jégou, Frédéric Chalmel, and Serge Nef. "Research Resource: The Dynamic Transcriptional Profile of Sertoli Cells During the Progression of Spermatogenesis." Molecular Endocrinology 29, no. 4 (April 1, 2015): 627–42. http://dx.doi.org/10.1210/me.2014-1356.
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Abstract Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.
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Zhang, Peng, Xiao-Ou Zhang, Tingting Jiang, Lingling Cai, Xiao Huang, Qi Liu, Dan Li, et al. "Comprehensive identification of alternative back-splicing in human tissue transcriptomes." Nucleic Acids Research 48, no. 4 (January 24, 2020): 1779–89. http://dx.doi.org/10.1093/nar/gkaa005.
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Abstract Circular RNAs (circRNAs) are covalently closed RNAs derived from back-splicing of genes across eukaryotes. Through alternative back-splicing (ABS), a single gene produces multiple circRNAs sharing the same back-splice site. Although many ABS events have recently been discovered, to what extent ABS involves in circRNA biogenesis and how it is regulated in different human tissues still remain elusive. Here, we reported an in-depth analysis of ABS events in 90 human tissue transcriptomes. We observed that ABS occurred for about 84% circRNAs. Interestingly, alternative 5′ back-splicing occurs more prevalently than alternative 3′ back-splicing, and both of them are tissue-specific, especially enriched in brain tissues. In addition, the patterns of ABS events in different brain regions are similar to each other and are more complex than the patterns in non-brain tissues. Finally, the intron length and abundance of Alu elements positively correlated with ABS event complexity, and the predominant circRNAs had longer flanking introns and more Alu elements than other circRNAs in the same ABS event. Together, our results represent a resource for circRNA research—we expanded the repertoire of ABS events of circRNAs in human tissue transcriptomes and provided insights into the complexity of circRNA biogenesis, expression, and regulation.
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Eck, Franziska, Santosh Phuyal, Matthew D. Smith, Manuel Kaulich, Simon Wilkinson, Hesso Farhan, and Christian Behrends. "ACSL3 is a novel GABARAPL2 interactor that links ufmylation and lipid droplet biogenesis." Journal of Cell Science 133, no. 18 (August 25, 2020): jcs243477. http://dx.doi.org/10.1242/jcs.243477.
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ABSTRACTWhile studies of the autophagy-related (ATG) genes in knockout models have led to an explosion of knowledge about the functions of autophagy components, the exact roles of LC3 and GABARAP family proteins (human ATG8 equivalents) are still poorly understood. A major drawback in understanding their roles is that the available interactome data has largely been acquired using overexpression systems. To overcome these limitations, we employed CRISPR/Cas9-based genome-editing to generate a panel of cells in which human ATG8 genes were tagged at their natural chromosomal locations with an N-terminal affinity epitope. This cellular resource was employed to map endogenous GABARAPL2 protein complexes using interaction proteomics. This approach identified the ER-associated protein and lipid droplet (LD) biogenesis factor ACSL3 as a stabilizing GABARAPL2-binding partner. GABARAPL2 bound ACSL3 in a manner dependent on its LC3-interacting regions, whose binding site in GABARAPL2 was required to recruit the latter to the ER. Through this interaction, the UFM1-activating enzyme UBA5 became anchored at the ER. Furthermore, ACSL3 depletion and LD induction affected the abundance of several ufmylation components and ER-phagy. Together these data allow us to define ACSL3 as a novel regulator of the enigmatic UFM1 conjugation pathway.
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Cockman, Eric, Paul Anderson, and Pavel Ivanov. "TOP mRNPs: Molecular Mechanisms and Principles of Regulation." Biomolecules 10, no. 7 (June 27, 2020): 969. http://dx.doi.org/10.3390/biom10070969.
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The cellular response to changes in the surrounding environment and to stress requires the coregulation of gene networks aiming to conserve energy and resources. This is often achieved by downregulating protein synthesis. The 5’ Terminal OligoPyrimidine (5’ TOP) motif-containing mRNAs, which encode proteins that are essential for protein synthesis, are the primary targets of translational control under stress. The TOP motif is a cis-regulatory RNA element that begins directly after the m7G cap structure and contains the hallmark invariant 5’-cytidine followed by an uninterrupted tract of 4–15 pyrimidines. Regulation of translation via the TOP motif coordinates global protein synthesis with simultaneous co-expression of the protein components required for ribosome biogenesis. In this review, we discuss architecture of TOP mRNA-containing ribonucleoprotein complexes, the principles of their assembly, and the modes of regulation of TOP mRNA translation.
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Li, Shengxing, Haiying Liang, Liang Tao, Liquan Xiong, Wenhui Liang, Zhuogong Shi, and Zhiheng Zhao. "Transcriptome Sequencing and Differential Expression Analysis Reveal Molecular Mechanisms for Starch Accumulation in Chestnut." Forests 11, no. 4 (April 1, 2020): 388. http://dx.doi.org/10.3390/f11040388.
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Chestnuts are popular edible nuts that are rich in starch. In order to enhance the transcriptomic resources and further understand starch and sucrose metabolism in maturing chestnuts, a comparative transcriptomic study of Chinese chestnut kernels was conducted at three ripening stages (70, 82, and 94 DAF). At 82 and 94 days after flowering (DAF), starch continued to accumulate, and the amylopectin/amylose ratio increased. Transcriptomic profiling of kernels at 70 (stage I), 82 (stage II), and 94 DAF (stage III) indicated that soluble starch synthase and α-1,4-glucan branching enzyme genes are actively expressed at 82 and 94 DAF. The starch degradation enzymes amylase, phosphoglucan phosphatase DSP4, and maltose exporter did not show differential gene expression, while glycogen phosphorylase-encoding unigenes were significantly down-regulated at 94 DAF. In addition to starch and sucrose metabolism, RNA transport, RNA degradation, pyrimidine metabolism, purine metabolism, plant hormone signal transduction, plant–pathogen interactions, and glycerophospholipid metabolism were found to be significantly enriched in all comparisons included in the study. As Chinese chestnut matured, the unique enriched pathways switched from ribosomal biogenesis and RNA polymerase of eukaryotes to endocytosis and spliceosomes. These genomic resources and findings are valuable for further understanding starch and sucrose metabolism in the Chinese chestnut.
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Shishodia, Sonia Kumari, and Jata Shankar. "Exploration of Mycelial Proteins from Aspergillus terreus Revealed Ribosome Biogenesis and Antioxidant Enzymes." Current Proteomics 17, no. 5 (July 16, 2020): 433–45. http://dx.doi.org/10.2174/1570164617666191004163734.
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Background: Aspergillus terreus is a major etiological agent among fungal pathogens and emerged as an opportunistic pathogen in immunocompromised patients. Methods: The mycelial proteins of A. terreus cultured for 48h at 37°C have been analysed by using nLC-ESI-MS/MS. Protein data analysis performed by Proteome Discoverer (V/2.2) against the UniProt database. Also, Scanning Electron Microscopy (SEM) analysis of biofilm formation under optimum conditions was carried out. qRT-PCR was carried out for genes encoding for functionally important proteins. Results: A total of 389 proteins were detected at FDR 0.01. Gene ontology showed the abundance of proteins from energy metabolism, cellular homeostasis, ribosome biogenesis, cell wall, and structural components. We observed catalase, superoxide dismutase, thioredoxin, glutathione S-transferase involved in redox homeostasis and heat shock proteins (Hsp90 and Hsp70). These proteins may provide insight into the resistance mechanism of A. terreus against AmB. Additionally, SEM analysis of A. terreus showed the formation of dense hyphal network covered with porous extracellular matrix (ECM). Using SECRETOOL, 8 proteins were predicted as secretory. Three proteins, such as glucanase Crf1/allergen (Asp F9), 1, 3-β-glucanosyltransferase and β-hexosaminidase were reported in biofilm establishment. Conclusion: Our proteome data provided experimental evidence to the annotated set of proteins in A. terreus that comprehend biochemical and cellular events involved in the establishment of mycelial network and contributing to the pathogenesis. This work also provides resource for further molecular studies in A. terreus.
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Lehmann, Marcus, Annie K. Burton, Savannah G. Szemethy, Jorge Valdez, and Jonathan N. Thon. "In Vitro Functionality of hiPSC Derived PLT+: The Utility of Microfluidic Assays in Determining Potency." Blood 134, Supplement_1 (November 13, 2019): 1168. http://dx.doi.org/10.1182/blood-2019-131896.
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Introduction: There is a growing shortage of platelets, the principal blood cells responsible for clot formation and blood vessel repair at sites of active bleeding. Platelet BioGenesis (PBG) is developing a commercial-scale, donor-free platelet (PLT+) production process using a cGMP-grade human induced pluripotent stem cell line (hiPSC) to address this issue. The PLT+ activity is being characterized extensively through multiple approaches that measure hemostatic function both in vitro and in vivo, with the ultimate goal of determining a clinical dose in humans. Alongside tests such as the current gold standard thrombin generation assay (TGA), we have developed an in-house microfluidic model to measure the ability of PLT+ to adhere to extracellular proteins under flow. The assay captures the surface receptor dynamics, as well as the ability of PLT+ to initiate coagulation. Materials and Methods: The thrombin generation assays are performed according to manufacturer's instructions. For the in-house microfluidic assay (MFA), fibrillar collagen, fibrinogen, or von Willebrand Factor is patterned in a commercial microfluidic device (Ibidi Slide VI 0.1). PLT+ (DNA-, calcein +, CD61+, CD42a+ cells from our bioreactor) are concentrated in normal pooled plasma, platelet additive solution, or platelet wash buffer to a normalized concentration of 1e8/mL, and are labeled with the mitochondrial dye DiOC6. Calcium chloride (7.5 mM) is added and the solution is perfused with a syringe pump at 50 1/s over the bioactive surface for 10 min. Images are captured every 10 seconds and quantified with ImageJ. After perfusion, the samples are fixed with 4% paraformaldehyde and can be stained for further characterization. Results and Discussion: PLTs+ are functionally non-inferior to human donor (blood) platelets and appear more active than Day 4/5 stored apheresis unit platelets. The TGA of PLT+ shows a more rapid generation of thrombin but similar total potential to donor platelets (Figure A). In the microfluidic assay, PLT+ (green DiOC6, red PAC1, figure B) adhere readily to the collagen surface under low shear flow, but do not adhere to non-functionalized surfaces, indicating GPVI functionality. As measured by surface coverage, the PLT+ resuspended in PAS adhere faster to the surface than either freshly washed donor platelets or apheresis platelets (p=0.01). When the PLT+ are preincubated in normal pooled plasma prior to perfusion, we observe fibrin formation and the aggregates show clot retraction, which supports the TGA results. Adhesion to surface bound fibrinogen and VWF is also comparable to donor platelets (GP IIb/IIa and GPIb function,). Combined, the TGA and MFA data reflect results of traditional more resource intensive assays, suggesting their viability as a rapid and flexible platform to study platelet function and function as release assays for in vitro generated PLTs+ Conclusion: Current work demonstrates that PLT+ are functional and a future alternative to donor derived platelet units. The MFA is a valuable tool for the characterization of this new therapeutic because of its specific control of surface protein-receptor interactions, shear forces, and flexibility to look at multiple markers. Alongside the TGA, the MFA will be a release assay for the PLT+. Figure Disclosures Lehmann: Platelet Biogenesis: Employment. Burton:Platelet Biogenesis: Employment. Szemethy:Platelet Biogenesis: Employment. Valdez:Platelet BioGenesis: Employment. Thon:Platelet BioGenesis: Employment.
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Suganuma, Tamaki, and Jerry L. Workman. "Chromatin and Metabolism." Annual Review of Biochemistry 87, no. 1 (June 20, 2018): 27–49. http://dx.doi.org/10.1146/annurev-biochem-062917-012634.
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Chromatin is a mighty consumer of cellular energy generated by metabolism. Metabolic status is efficiently coordinated with transcription and translation, which also feed back to regulate metabolism. Conversely, suppression of energy utilization by chromatin processes may serve to preserve energy resources for cell survival. Most of the reactions involved in chromatin modification require metabolites as their cofactors or coenzymes. Therefore, the metabolic status of the cell can influence the spectra of posttranslational histone modifications and the structure, density and location of nucleosomes, impacting epigenetic processes. Thus, transcription, translation, and DNA/RNA biogenesis adapt to cellular metabolism. In addition to dysfunctions of metabolic enzymes, imbalances between metabolism and chromatin activities trigger metabolic disease and life span alteration. Here, we review the synthesis of the metabolites and the relationships between metabolism and chromatin function. Furthermore, we discuss how the chromatin response feeds back to metabolic regulation in biological processes.
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Shalit-Kaneh, Akiva, Tamar Eviatar-Ribak, Guy Horev, Naomi Suss, Roni Aloni, Yuval Eshed, and Eliezer Lifschitz. "The flowering hormone florigen accelerates secondary cell wall biogenesis to harmonize vascular maturation with reproductive development." Proceedings of the National Academy of Sciences 116, no. 32 (July 19, 2019): 16127–36. http://dx.doi.org/10.1073/pnas.1906405116.
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Florigen, a proteinaceous hormone, functions as a universal long-range promoter of flowering and concurrently as a generic growth-attenuating hormone across leaf and stem meristems. In flowering plants, the transition from the vegetative phase to the reproductive phase entails the orchestration of new growth coordinates and a global redistribution of resources, signals, and mechanical loads among organs. However, the ultimate cellular processes governing the adaptation of the shoot system to reproduction remain unknown. We hypothesized that if the mechanism for floral induction is universal, then the cellular metabolic mechanisms underlying the conditioning of the shoot system for reproduction would also be universal and may be best regulated by florigen itself. To understand the cellular basis for the vegetative functions of florigen, we explored the radial expansion of tomato stems. RNA-Seq and complementary genetic and histological studies revealed that florigen of endogenous, mobile, or induced origins accelerates the transcription network navigating secondary cell wall biogenesis as a unit, promoting vascular maturation and thereby adapting the shoot system to the developmental needs of the ensuing reproductive phase it had originally set into motion. We then demonstrated that a remarkably stable and broadly distributed florigen promotes MADS and MIF genes, which in turn regulate the rate of vascular maturation and radial expansion of stems irrespective of flowering or florigen level. The dual acceleration of flowering and vascular maturation by florigen provides a paradigm for coordinated regulation of independent global developmental programs.
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Lu, Yuan-Ping, Jian-Hua Liao, Zhong-Jie Guo, Zhi-Xin Cai, and Mei-Yuan Chen. "Genome Survey and Transcriptome Analysis on Mycelia and Primordia of Agaricus blazei." BioMed Research International 2020 (January 14, 2020): 1–12. http://dx.doi.org/10.1155/2020/1824183.
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Agaricus blazei, a type of edible straw-rotting mushroom with somewhat sweet taste and fragrance of almonds, has attracted considerable scientific and practical attention. High-throughput Illumina PE150 and PacBio RSII platform were employed to generate a genomic sequence. De novo assembly generated 36 contigs with 38,686,133 bp in size, containing 10,119 putative predicted genes. Additionally, we also studied transcriptional regulation of the mycelia and the primordia for exploration of genes involved in fruiting body formation. Expression profiling analysis revealed that 2,164 genes were upregulated in mycelia and 1,557 in primordia. Functional enrichment showed that differentially expressed genes associated with response to stress, ribosome biogenesis, arginine biosynthesis, and steroid biosynthesis pathway were more active in fruiting body. The genome and transcriptome analysis of A. blazei provide valuable sequence resources and contribute to our understanding of genes related to the biosynthesis pathway of polysaccharide and benzaldehyde, as well as the fruiting body formation.
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Tang, Min, Ling Kui, Guanyi Lu, and Wenqiang Chen. "Disease-Associated Circular RNAs: From Biology to Computational Identification." BioMed Research International 2020 (August 18, 2020): 1–21. http://dx.doi.org/10.1155/2020/6798590.
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Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed continuous loop, generated through various backsplicing events of pre-mRNA. An accumulating number of studies have shown that circRNAs are potential biomarkers for major human diseases such as cancer and Alzheimer’s disease. Thus, identification and prediction of human disease-associated circRNAs are of significant importance. To this end, a computational analysis-assisted strategy is indispensable to detect, verify, and quantify circRNAs for downstream applications. In this review, we briefly introduce the biology of circRNAs, including the biogenesis, characteristics, and biological functions. In addition, we outline about 30 recent bioinformatic analysis tools that are publicly available for circRNA study. Principles for applying these computational strategies and considerations will be briefly discussed. Lastly, we give a complete survey on more than 20 key computational databases that are frequently used. To our knowledge, this is the most complete and updated summary on publicly available circRNA resources. In conclusion, this review summarizes key aspects of circRNA biology and outlines key computational strategies that will facilitate the genome-wide identification and prediction of circRNAs.
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Liu, Chun-Jie, Xin Fu, Mengxuan Xia, Qiong Zhang, Zhifeng Gu, and An-Yuan Guo. "miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets." Nucleic Acids Research 49, no. D1 (September 29, 2020): D1276—D1281. http://dx.doi.org/10.1093/nar/gkaa783.
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Abstract MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3′UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.
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Lee, Seon-Jin, Jinglan Zhang, Augustine M. K. Choi, and Hong Pyo Kim. "Mitochondrial Dysfunction Induces Formation of Lipid Droplets as a Generalized Response to Stress." Oxidative Medicine and Cellular Longevity 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/327167.
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Lipid droplet (LD) formation is a hallmark of cellular stress. Cells attempt to combat noxious stimuli by switching their metabolism from oxidative phosphorylation to glycolysis, sparing resources in LDs for generating cellular reducing power and for anabolic biosynthesis. Membrane phospholipids are also a source of LDs. To elucidate the formation of LDs, we exposed mice to hyperoxia, hypoxia, myocardial ischemia, and sepsis induced by cecal ligation and puncture (CLP). All the above-mentioned stressors enhanced the formation of LDs, as assessed by transmission electron microscopy, with severe mitochondrial swelling. Disruption of mitochondria by depleting mitochondrial DNA (ρ0 cells) significantly augmented the formation of LDs, causing transcriptional activation of fatty acid biosynthesis and metabolic reprogramming to glycolysis. Heme oxygenase (HO)-1 counteracts CLP-mediated septic shock in mouse models. In HO-1-deficient mice, LD formation was not observed upon CLP, but a concomitant decrease in “LD-decorating proteins” was observed, implying a link between LDs and cytoprotective activity. Collectively, LD biogenesis during stress can trigger adaptive LD formation, which is dependent on mitochondrial integrity and HO-1 activity; this may be a cellular survival strategy, apportioning energy-generating substrates to cellular defense.
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Zhang, Minzhe, Tao Wang, Guanghua Xiao, and Yang Xie. "Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets." Genes 11, no. 1 (January 3, 2020): 54. http://dx.doi.org/10.3390/genes11010054.
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Circular RNAs are a special type of RNA that has recently attracted a lot of research interest in studying its formation and function. RNA binding proteins (RBPs) that bind circRNAs are important in these processes, but have been relatively less studied. CLIP-Seq technology has been invented and applied to profile RBP-RNA interactions on the genome-wide scale. While mRNAs are usually the focus of CLIP-Seq experiments, RBP-circRNA interactions could also be identified through specialized analysis of CLIP-Seq datasets. However, many technical difficulties are involved in this process, such as the usually short read length of CLIP-Seq reads. In this study, we created a pipeline called Clirc specialized for profiling circRNAs in CLIP-Seq data and analyzing the characteristics of RBP-circRNA interactions. In conclusion, to our knowledge, this is one of the first studies to investigate circRNAs and their binding partners through repurposing CLIP-Seq datasets, and we hope our work will become a valuable resource for future studies into the biogenesis and function of circRNAs.
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Mielecki, Jakub, Piotr Gawroński, and Stanisław Karpiński. "Retrograde Signaling: Understanding the Communication between Organelles." International Journal of Molecular Sciences 21, no. 17 (August 26, 2020): 6173. http://dx.doi.org/10.3390/ijms21176173.
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Understanding how cell organelles and compartments communicate with each other has always been an important field of knowledge widely explored by many researchers. However, despite years of investigations, one point—and perhaps the only point that many agree on—is that our knowledge about cellular-signaling pathways still requires expanding. Chloroplasts and mitochondria (because of their primary functions in energy conversion) are important cellular sensors of environmental fluctuations and feedback they provide back to the nucleus is important for acclimatory responses. Under stressful conditions, it is important to manage cellular resources more efficiently in order to maintain a proper balance between development, growth and stress responses. For example, it can be achieved through regulation of nuclear and organellar gene expression. If plants are unable to adapt to stressful conditions, they will be unable to efficiently produce energy for growth and development—and ultimately die. In this review, we show the importance of retrograde signaling in stress responses, including the induction of cell death and in organelle biogenesis. The complexity of these pathways demonstrates how challenging it is to expand the existing knowledge. However, understanding this sophisticated communication may be important to develop new strategies of how to improve adaptability of plants in rapidly changing environments.
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de Sousa-d’Auria, Célia, Florence Constantinesco-Becker, Patricia Constant, Maryelle Tropis, and Christine Houssin. "Genome-wide identification of novel genes involved in Corynebacteriales cell envelope biogenesis using Corynebacterium glutamicum as a model." PLOS ONE 15, no. 12 (December 31, 2020): e0240497. http://dx.doi.org/10.1371/journal.pone.0240497.
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Corynebacteriales are Actinobacteria that possess an atypical didermic cell envelope. One of the principal features of this cell envelope is the presence of a large complex made up of peptidoglycan, arabinogalactan and mycolic acids. This covalent complex constitutes the backbone of the cell wall and supports an outer membrane, called mycomembrane in reference to the mycolic acids that are its major component. The biosynthesis of the cell envelope of Corynebacteriales has been extensively studied, in particular because it is crucial for the survival of important pathogens such as Mycobacterium tuberculosis and is therefore a key target for anti-tuberculosis drugs. In this study, we explore the biogenesis of the cell envelope of Corynebacterium glutamicum, a non-pathogenic Corynebacteriales, which can tolerate dramatic modifications of its cell envelope as important as the loss of its mycomembrane. For this purpose, we used a genetic approach based on genome-wide transposon mutagenesis. We developed a highly effective immunological test based on the use of anti-cell wall antibodies that allowed us to rapidly identify bacteria exhibiting an altered cell envelope. A very large number (10,073) of insertional mutants were screened by means of this test, and 80 were finally selected, representing 55 different loci. Bioinformatics analyses of these loci showed that approximately 60% corresponded to genes already characterized, 63% of which are known to be directly involved in cell wall processes, and more specifically in the biosynthesis of the mycoloyl-arabinogalactan-peptidoglycan complex. We identified 22 new loci potentially involved in cell envelope biogenesis, 76% of which encode putative cell envelope proteins. A mutant of particular interest was further characterized and revealed a new player in mycolic acid metabolism. Because a large proportion of the genes identified by our study is conserved in Corynebacteriales, the library described here provides a new resource of genes whose characterization could lead to a better understanding of the biosynthesis of the envelope components of these bacteria.
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Kuang, Gangqiao, Wenjing Tao, Shuqing Zheng, Xiaoshuang Wang, and Deshou Wang. "Genome-Wide Identification, Evolution and Expression of the Complete Set of Cytoplasmic Ribosomal Protein Genes in Nile Tilapia." International Journal of Molecular Sciences 21, no. 4 (February 12, 2020): 1230. http://dx.doi.org/10.3390/ijms21041230.
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Ribosomal proteins (RPs) are indispensable in ribosome biogenesis and protein synthesis, and play a crucial role in diverse developmental processes. In the present study, we carried out a comprehensive analysis of RPs in chordates and examined the expression profiles of the complete set of 92 cytoplasmic RP genes in Nile tilapia. The RP genes were randomly distributed throughout the tilapia genome. Phylogenetic and syntenic analyses revealed the existence of duplicated RP genes from 2R (RPL3, RPL7, RPL22 and RPS27) and 3R (RPL5, RPL19, RPL22, RPL41, RPLP2, RPS17, RPS19 and RPS27) in tilapia and even more from 4R in common carp and Atlantic salmon. The RP genes were found to be expressed in all tissues examined, but their expression levels differed among different tissues. Gonadal transcriptome analysis revealed that almost all RP genes were highly expressed, and their expression levels were highly variable between ovaries and testes at different developmental stages in tilapia. No sex- and stage-specific RP genes were found. Eleven RP genes displayed sexually dimorphic expression with nine higher in XY gonad and two higher in XX gonad at all stages examined, which were proved to be phenotypic sex dependent. Quantitative real-time PCR and immunohistochemistry ofRPL5b and RPL24 were performed to validate the transcriptome data. The genomic resources and expression data obtained in this study will contribute to a better understanding of RPs evolution and functions in chordates.
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Dori, Martina, Leila Haj Abdullah Alieh, Daniel Cavalli, Simone Massalini, Mathias Lesche, Andreas Dahl, and Federico Calegari. "Sequence and expression levels of circular RNAs in progenitor cell types during mouse corticogenesis." Life Science Alliance 2, no. 2 (March 29, 2019): e201900354. http://dx.doi.org/10.26508/lsa.201900354.
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Circular (circ) RNAs have recently emerged as a novel class of transcripts whose identification and function remain elusive. Among many tissues and species, the mammalian brain is the organ in which circRNAs are more abundant and first evidence of their functional significance started to emerge. Yet, even within this well-studied organ, annotation of circRNAs remains fragmentary, their sequence is unknown, and their expression in specific cell types was never investigated. Overcoming these limitations, here we provide the first comprehensive identification of circRNAs and assessment of their expression patterns in proliferating neural stem cells, neurogenic progenitors, and newborn neurons of the developing mouse cortex. Extending the current knowledge about the diversity of this class of transcripts by the identification of nearly 4,000 new circRNAs, our study is the first to provide the full sequence information and expression patterns of circRNAs in cell types representing the lineage of neurogenic commitment. We further exploited our data by evaluating the coding potential, evolutionary conservation, and biogenesis of circRNAs that we found to arise from a specific subclass of linear mRNAs. Our study provides the arising field of circRNA biology with a powerful new resource to address the complexity and potential biological significance of this new class of transcripts.
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Dragomir, Mihnea P., Ganiraju C. Manyam, Leonie Florence Ott, Léa Berland, Erik Knutsen, Cristina Ivan, Leonard Lipovich, Bradley M. Broom, and George A. Calin. "FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs." Non-Coding RNA 6, no. 4 (September 23, 2020): 41. http://dx.doi.org/10.3390/ncrna6040041.
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Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually becoming appreciated as a new class of functional molecules that contribute to diverse cellular processes, and are deregulated in different diseases contributing to pathogenesis. As multiple publications have identified unique ncPEPs, we appreciated the need for assembling a new web resource that could gather information about these functional ncPEPs. We developed FuncPEP, a new database of functional ncRNA encoded peptides, containing all experimentally validated and functionally characterized ncPEPs. Currently, FuncPEP includes a comprehensive annotation of 112 functional ncPEPs and specific details regarding the ncRNA transcripts that encode these peptides. We believe that FuncPEP will serve as a platform for further deciphering the biologic significance and medical use of ncPEPs. The link for FuncPEP database can be found at the end of the Introduction Section.
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Romanowski, Andrés, James J. Furniss, Ejaz Hussain, and Karen J. Halliday. "Phytochrome regulates cellular response plasticity and the basic molecular machinery of leaf development." Plant Physiology 186, no. 2 (March 9, 2021): 1220–39. http://dx.doi.org/10.1093/plphys/kiab112.
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Abstract Plants are plastic organisms that optimize growth in response to a changing environment. This adaptive capability is regulated by external cues, including light, which provides vital information about the habitat. Phytochrome photoreceptors detect far-red light, indicative of nearby vegetation, and elicit the adaptive shade-avoidance syndrome (SAS), which is critical for plant survival. Plants exhibiting SAS are typically more elongated, with distinctive, small, narrow leaf blades. By applying SAS-inducing end-of-day far-red (EoD FR) treatments at different times during Arabidopsis (Arabidopsis thaliana) leaf 3 development, we have shown that SAS restricts leaf blade size through two distinct cellular strategies. Early SAS induction limits cell division, while later exposure limits cell expansion. This flexible strategy enables phytochromes to maintain control of leaf size through the proliferative and expansion phases of leaf growth. mRNAseq time course data, accessible through a community resource, coupled to a bioinformatics pipeline, identified pathways that underlie these dramatic changes in leaf growth. Phytochrome regulates a suite of major development pathways that control cell division, expansion, and cell fate. Further, phytochromes control cell proliferation through synchronous regulation of the cell cycle, DNA replication, DNA repair, and cytokinesis, and play an important role in sustaining ribosome biogenesis and translation throughout leaf development.
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Kumar, Gokhlesh, Reinhard Ertl, Jerri L. Bartholomew, and Mansour El-Matbouli. "Transcriptome Analysis Elucidates the Key Responses of Bryozoan Fredericella sultana during the Development of Tetracapsuloides bryosalmonae (Myxozoa)." International Journal of Molecular Sciences 21, no. 16 (August 17, 2020): 5910. http://dx.doi.org/10.3390/ijms21165910.
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Bryozoans are sessile, filter-feeding, and colony-building invertebrate organisms. Fredericella sultana is a well known primary host of the myxozoan parasite Tetracapsuloides bryosalmonae. There have been no attempts to identify the cellular responses induced in F. sultana during the T. bryosalmonae development. We therefore performed transcriptome analysis with the aim of identifying candidate genes and biological pathways of F. sultana involved in the response to T. bryosalmonae. A total of 1166 differentially up- and downregulated genes were identified in the infected F. sultana. Gene ontology of biological processes of upregulated genes pointed to the involvement of the innate immune response, establishment of protein localization, and ribosome biogenesis, while the downregulated genes were involved in mitotic spindle assembly, viral entry into the host cell, and response to nitric oxide. Eukaryotic Initiation Factor 2 signaling was identified as a top canonical pathway and MYCN as a top upstream regulator in the differentially expressed genes. Our study provides the first transcriptional profiling data on the F. sultana zooid’s response to T. bryosalmonae. Pathways and upstream regulators help us to understand the complex interplay in the infected F. sultana. The results will facilitate the elucidation of innate immune mechanisms of bryozoan and will lay a foundation for further analyses on bryozoan-responsive candidate genes, which will be an important resource for the comparative analysis of gene expression in bryozoans.
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Thazar-Poulot, Nelcy, Martine Miquel, Isabelle Fobis-Loisy, and Thierry Gaude. "Peroxisome extensions deliver the Arabidopsis SDP1 lipase to oil bodies." Proceedings of the National Academy of Sciences 112, no. 13 (March 16, 2015): 4158–63. http://dx.doi.org/10.1073/pnas.1403322112.
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Lipid droplets/oil bodies (OBs) are lipid-storage organelles that play a crucial role as an energy resource in a variety of eukaryotic cells. Lipid stores are mobilized in the case of food deprivation or high energy demands—for example, during certain developmental processes in animals and plants. OB degradation is achieved by lipases that hydrolyze triacylglycerols (TAGs) into free fatty acids and glycerol. In the model plant Arabidopsis thaliana, Sugar-Dependent 1 (SDP1) was identified as the major TAG lipase involved in lipid reserve mobilization during seedling establishment. Although the enzymatic activity of SDP1 is associated with the membrane of OBs, its targeting to the OB surface remains uncharacterized. Here we demonstrate that the core retromer, a complex involved in protein trafficking, participates in OB biogenesis, lipid store degradation, and SDP1 localization to OBs. We also report an as-yet-undescribed mechanism for lipase transport in eukaryotic cells, with SDP1 being first localized to the peroxisome membrane at early stages of seedling growth and then possibly moving to the OB surface through peroxisome tubulations. Finally, we show that the timely transfer of SDP1 to the OB membrane requires a functional core retromer. In addition to revealing previously unidentified functions of the retromer complex in plant cells, our work provides unanticipated evidence for the role of peroxisome dynamics in interorganelle communication and protein transport.
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Srinivasan, Rajalakshmi, Adhish S. Walvekar, Zeenat Rashida, Aswin Seshasayee, and Sunil Laxman. "Genome-scale reconstruction of Gcn4/ATF4 networks driving a growth program." PLOS Genetics 16, no. 12 (December 30, 2020): e1009252. http://dx.doi.org/10.1371/journal.pgen.1009252.
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Growth and starvation are considered opposite ends of a spectrum. To sustain growth, cells use coordinated gene expression programs and manage biomolecule supply in order to match the demands of metabolism and translation. Global growth programs complement increased ribosomal biogenesis with sufficient carbon metabolism, amino acid and nucleotide biosynthesis. How these resources are collectively managed is a fundamental question. The role of the Gcn4/ATF4 transcription factor has been best studied in contexts where cells encounter amino acid starvation. However, high Gcn4 activity has been observed in contexts of rapid cell proliferation, and the roles of Gcn4 in such growth contexts are unclear. Here, using a methionine-induced growth program in yeast, we show that Gcn4/ATF4 is the fulcrum that maintains metabolic supply in order to sustain translation outputs. By integrating matched transcriptome and ChIP-Seq analysis, we decipher genome-wide direct and indirect roles for Gcn4 in this growth program. Genes that enable metabolic precursor biosynthesis indispensably require Gcn4; contrastingly ribosomal genes are partly repressed by Gcn4. Gcn4 directly binds promoter-regions and transcribes a subset of metabolic genes, particularly driving lysine and arginine biosynthesis. Gcn4 also globally represses lysine and arginine enriched transcripts, which include genes encoding the translation machinery. The Gcn4 dependent lysine and arginine supply thereby maintains the synthesis of the translation machinery. This is required to maintain translation capacity. Gcn4 consequently enables metabolic-precursor supply to bolster protein synthesis, and drive a growth program. Thus, we illustrate how growth and starvation outcomes are both controlled using the same Gcn4 transcriptional outputs that function in distinct contexts.
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Ylla, Guillem, Tianyuan Liu, and Ana Conesa. "MirCure: a tool for quality control, filter and curation of microRNAs of animals and plants." Bioinformatics 36, Supplement_2 (December 2020): i618—i624. http://dx.doi.org/10.1093/bioinformatics/btaa889.
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Abstract Motivation microRNAs (miRNAs) are essential components of gene expression regulation at the post-transcriptional level. miRNAs have a well-defined molecular structure and this has facilitated the development of computational and high-throughput approaches to predict miRNAs genes. However, due to their short size, miRNAs have often been incorrectly annotated in both plants and animals. Consequently, published miRNA annotations and miRNA databases are enriched for false miRNAs, jeopardizing their utility as molecular information resources. To address this problem, we developed MirCure, a new software for quality control, filtering and curation of miRNA candidates. MirCure is an easy-to-use tool with a graphical interface that allows both scoring of miRNA reliability and browsing of supporting evidence by manual curators. Results Given a list of miRNA candidates, MirCure evaluates a number of miRNA-specific features based on gene expression, biogenesis and conservation data, and generates a score that can be used to discard poorly supported miRNA annotations. MirCure can also curate and adjust the annotation of the 5p and 3p arms based on user-provided small RNA-seq data. We evaluated MirCure on a set of manually curated animal and plant miRNAs and demonstrated great accuracy. Moreover, we show that MirCure can be used to revisit previous bona fide miRNAs annotations to improve miRNA databases. Availability and implementation The MirCure software and all the additional scripts used in this project are publicly available at https://github.com/ConesaLab/MirCure. A Docker image of MirCure is available at https://hub.docker.com/r/conesalab/mircure. Supplementary information Supplementary data are available at Bioinformatics online.
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Manola, Maria S., Eleni N. Tsakiri, and Ioannis P. Trougakos. "Alterations in Organismal Physiology, Impaired Stress Resistance, and Accelerated Aging in Drosophila Flies Adapted to Multigenerational Proteome Instability." Oxidative Medicine and Cellular Longevity 2019 (June 11, 2019): 1–14. http://dx.doi.org/10.1155/2019/7823285.
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Being an assembly of highly sophisticated protein machines, cells depend heavily on proteostatic modules functionality and on adequate supply of energetic molecules for maintaining proteome stability. Yet, our understanding of the adaptations induced by multigenerational proteotoxic stress is limited. We report here that multigenerational (>80 generations) proteotoxic stress in OregonR flies induced by constant exposure to developmentally nonlethal doses of the proteasome inhibitor bortezomib (BTZ) (G80-BTZ flies) increased proteome instability and redox imbalance, reduced fecundity and body size, and caused neuromuscular defects; it also accelerated aging. G80-BTZ flies were mildly resistant to increased doses of BTZ and showed no age-related loss of proteasome activity; these adaptations correlated with sustained upregulation of proteostatic modules, which however occurred at the cost of minimal responses to increased BTZ doses and increased susceptibility to various types of additional proteotoxic stress, namely, autophagy inhibition or thermal stress. Multigenerational proteome instability and redox imbalance also caused metabolic reprogramming being evidenced by altered mitochondrial biogenesis and suppressed insulin/IGF-like signaling (IIS) in G80-BTZ flies. The toxic effects of multigenerational proteome instability could be partially mitigated by a low-protein diet that extended G80-BTZ flies’ longevity. Overall, persistent proteotoxic stress triggers a highly conserved adaptive metabolic response mediated by the IIS pathway, which reallocates resources from growth and longevity to somatic preservation and stress tolerance. Yet, these trade-off adaptations occur at the cost of accelerated aging and/or reduced tolerance to additional stress, illustrating the limited buffering capacity of survival pathways.
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Wang, Guifeng, Yan Gao, Liwei Yang, and Jisen Shi. "Identification and analysis of differentially expressed genes in differentiating xylem of Chinese fir (Cunninghamia lanceolata) by suppression subtractive hybridization." Genome 50, no. 12 (December 2007): 1141–55. http://dx.doi.org/10.1139/g07-091.
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Wood is an important raw material for global industries with rapidly increasing demand. To isolate the genes differentially expressed during xylogenesis of Chinese fir ( Cunninghamia lanceolata (Lamb.) Hook.), we used a novel system. Forward and reverse subtracted cDNA libraries were constructed using the suppression subtractive hybridization method; for the forward library we used cDNA from the mutant Dugansha as the tester and cDNA from the wild-type clone Jurong 0 as the driver, and for the reverse library we used Jurong 0 cDNA as the tester and Dugansha cDNA as the driver. Transcriptional profiling was performed using a macroarray with 4 digoxigenin-labeled probes. We obtained 618 and 409 clones from the forward and the reverse subtracted library, respectively. A total of 405 unique expressed sequence tags (ESTs) were obtained. Forty percent of the ESTs exhibited homologies with proteins of known function and fell into 4 major classes: metabolism, cell wall biogenesis and remodeling, signal transduction, and stress. Real-time PCR was performed to confirm the results. The expression levels of 11 selected ESTs were consistent with both macroarray and real-time PCR results. The systematic analysis of genes involved in wood formation in Chinese fir provides valuable insights into the molecular mechanisms involved in xylem differentiation and is an important resource for forest research that can be directed toward understanding the genetic control of wood formation and future endeavors to modify wood and fiber properties for industrial use.
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Song, Seon Beom, and Eun Seong Hwang. "High Levels of ROS Impair Lysosomal Acidity and Autophagy Flux in Glucose-Deprived Fibroblasts by Activating ATM and Erk Pathways." Biomolecules 10, no. 5 (May 13, 2020): 761. http://dx.doi.org/10.3390/biom10050761.
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Under glucose deprivation, cells heavily mobilize oxidative phosphorylation to maintain energy homeostasis. This leads to the generation of high levels of ATP, as well as reactive oxygen species (ROS), from mitochondria. In nutrient starvation, autophagy is activated, likely to facilitate resource recycling, but recent studies suggest that autophagy flux is inhibited in cells undergoing glucose deprivation. In this study, we analyzed the status of autophagic flux in glucose-deprived human fibroblasts. Although lysosomes increased in quantity due in part to an increase of biogenesis, a large population of them suffered low acidity in the glucose-deprived cells. Autophagosomes also accumulated due to poor autolysis in these cells. A treatment of antioxidants not only restored lysosomal acidity but also released the flux blockade. The inhibition of ataxia telangiectasia mutated (ATM) serine/threonine kinase, which is activated by ROS, also attenuated the impairment of lysosomal acidity and autophagic flux, suggesting an effect of ROS that might be mediated through ATM activation. In addition, the activity of extracellular signal-regulated kinase (Erk) increased upon glucose deprivation, but this was also compromised by a treatment of antioxidants. Furthermore, the Erk inhibitor treatment also alleviated the failure in lysosomal acidity and autophagic flux. These together indicate that, upon glucose deprivation, cells undergo a failure of autophagy flux through an impairment of lysosomal acidity and that a high-level ROS-induced activation of Erk and ATM is involved in this impairment.
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Sureda, Manuel, Aurora Crespo-Jara, Ramon Gonzalez Manzano, Maria del Carmen Redal, Francisco Javier Garcia-Cases, Elena Mª Martinez Navarro, and Antonio Brugarolas. "Contribution of microarrays of gene expression (MAGE) to the definition of PET/CT as a qualified biomarker of early response in metastatic patients." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 11573. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11573.
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11573 Background: Proliferating cancer cells consume elevated quantity of glucose, converted into lactate regardless the presence of oxygen (Warburg effect). This effect has been useful for imaging metabolically active tumors with FDG-PET, although its use in early response is controversial. Molecular mechanisms of FDG uptake are not fully understood. We have used MAGE to determine the most relevant genes involved in FDG uptake. Methods: Fresh-frozen tumor biopsies and quantitative basal FDG-PET/CT were obtained from metastatic lesions in cancer patients. Total tumor RNA was hybridized to a whole human genome oligonucleotide microarray. Gene expression signature-based prediction, using the most relevant genes involved in FDG uptake measured by SUV, was finally determined by Partial Least Squares (PLS). The interpretation of biological phenomena (IBP) derived from the selected genes was made by means of different public statistical bioinformatics resources. Results: 71 patients with different histological diagnosis were included in the training cohort and 13 in the validation one. 909 probes correlated significantly with SUV: 333 positively and 576 negatively. A predictive signature based on these 909 probes was built using PLS-3, with an RMSE in the validation set of 0.645 (within the 95% CI of RMSE determined in the training set). In IBP, other biological processes were more relevant than glycolysis in FDG uptake: RNA processing, ribosome biogenesis, protein processing, cell adhesion, cytoskeleton organization, angiogenesis and autophagy. Conclusions: This PLS-3-built signature is the first reported one that can accurately predict SUV. FDG uptake is a complex phenomenon that involves multiple biological processes, confirming the value of PET/CT in early response.
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Kanno, Tatsuo, Peter Venhuizen, Ming-Tsung Wu, Phebe Chiou, Chia-Liang Chang, Maria Kalyna, Antonius J. M. Matzke, and Marjori Matzke. "A Collection of Pre-mRNA Splicing Mutants in Arabidopsis thaliana." G3: Genes|Genomes|Genetics 10, no. 6 (April 7, 2020): 1983–96. http://dx.doi.org/10.1534/g3.119.400998.
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To investigate factors influencing pre-mRNA splicing in plants, we conducted a forward genetic screen using an alternatively-spliced GFP reporter gene in Arabidopsis thaliana. This effort generated a collection of sixteen mutants impaired in various splicing-related proteins, many of which had not been recovered in any prior genetic screen or implicated in splicing in plants. The factors are predicted to act at different steps of the spliceosomal cycle, snRNP biogenesis pathway, transcription, and mRNA transport. We have described eleven of the mutants in recent publications. Here we present the final five mutants, which are defective, respectively, in RNA-BINDING PROTEIN 45D (rbp45d), DIGEORGE SYNDROME CRITICAL REGION 14 (dgcr14), CYCLIN-DEPENDENT KINASE G2 (cdkg2), INTERACTS WITH SPT6 (iws1) and CAP BINDING PROTEIN 80 (cbp80). We provide RNA-sequencing data and analyses of differential gene expression and alternative splicing patterns for the cbp80 mutant and for several previously published mutants, including smfa and new alleles of cwc16a, for which such information was not yet available. Sequencing of small RNAs from the cbp80 mutant highlighted the necessity of wild-type CBP80 for processing of microRNA (miRNA) precursors into mature miRNAs. Redundancy tests of paralogs encoding several of the splicing factors revealed their functional non-equivalence in the GFP reporter gene system. We discuss the cumulative findings and their implications for the regulation of pre-mRNA splicing efficiency and alternative splicing in plants. The mutant collection provides a unique resource for further studies on a coherent set of splicing factors and their roles in gene expression, alternative splicing and plant development.
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Vainshtein, Anna, Liam D. Tryon, Marion Pauly, and David A. Hood. "Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle." American Journal of Physiology-Cell Physiology 308, no. 9 (May 1, 2015): C710—C719. http://dx.doi.org/10.1152/ajpcell.00380.2014.
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Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .
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Justice, Monica J., Ben T. Kile, and Lanette S. Woodward. "Inflammatory Disease and Abortive Platelet Shedding Caused by a Mutation in a Pivotal Regulator of Actin Dynamics in the redears Mouse." Blood 104, no. 11 (November 16, 2004): 1606. http://dx.doi.org/10.1182/blood.v104.11.1606.1606.
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Abstract Mouse mutagenesis using forward genetics is valuable as a gene function discovery tool. We are looking for blood defects in a large ENU mutagenesis screen, and have isolated many new mouse mutants that reveal new mechanisms in hematopoiesis. One mutant mouse strain, called redears, is an intriguing model of inflammatory disease and thrombocytopenia. Animals homozygous for the redears (rd) mutation develop spontaneous inflammatory lesions of the ears and tail characterized by neutrophil infiltration and peripheral neutrophila. Unexpectedly, blood platelet numbers are dramatically reduced in rd/rd animals. A thorough analysis of platelet biogenesis shows that the platelet precursor cell, the megakaryocyte, undergoes abnormal maturation, which results in gross morphological abnormalities, increased ploidy and abortive platelet shedding. Here we report a mutation in a novel gene related to the yeast actin-interacting protein Aip1 in rd/rd mice. In yeast, Aip1 interacts with, and increases the activity of cofilin, a key regulator of actin depolymerization. Our data confirm that actin dynamics are dysregulated in rd/rd megakaryocytes and neutrophils. The massive cytoplasmic reorganization that is required for megakaryocyte maturation and platelet shedding has long been assumed to depend on the actin cytoskeleton. Intriguingly, recent studies suggest the process is caspase-dependent, and represents a form of ‘para-apoptosis’. With this in mind, we found that chemotaxis and apoptosis are perturbed in rd/rd neutrophils, suggesting that neutrophils are playing a key role in driving the inflammation. Disrupted actin depolymerization would provide an explanation for chemotactic deficiencies. Further, recent evidence implicating cofilin and other actin regulators in the initiation of apoptosis would suggest that this novel protein may play an essential role in neutrophil cell death. Thus, the redears mouse not only provides the first in vivo demonstration of the critical role of the actin cytoskeleton in megakaryocyte development and platelet production, but also represents a unique reagent to examine the relationship between actin dynamics, cellular maturation, inflammation and apoptosis. Our ongoing mutagenesis efforts continue to reveal new developmental mechanisms. New mutants, genetic tools, and resources can be found at www.mouse-genome.bcm.tmc.edu