المؤلفون: Yu, Haiyang, Lu, Shan, Gasior, Kelsey, Singh, Digvijay, Vazquez-Sanchez, Sonia, Tapia, Olga, Toprani, Divek, Beccari, Melinda S, Yates, John R, Da Cruz, Sandrine, Newby, Jay M, Lafarga, Miguel, Gladfelter, Amy S, Villa, Elizabeth, Cleveland, Don W

المصدر: Science. 371(6529)

مصطلحات موضوعية: Neurosciences, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Aging, Animals, Anisotropy, Cryoelectron Microscopy, DNA-Binding Proteins, HEK293 Cells, HSP70 Heat-Shock Proteins, Histone Deacetylases, Humans, Liquid Crystals, Mice, Mice, Inbred C57BL, Mutation, Neurodegenerative Diseases, Neurons, Proteasome Endopeptidase Complex, Proteasome Inhibitors, Protein Aggregates, Protein Domains, RNA-Binding Proteins, Rats, Rats, Sprague-Dawley, General Science & Technology

الوصف: The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that RNA binding-deficient TDP-43 (produced by neurodegeneration-causing mutations or posttranslational acetylation in its RNA recognition motifs) drove TDP-43 demixing into intranuclear liquid spherical shells with liquid cores. These droplets, which we named "anisosomes", have shells that exhibit birefringence, thus indicating liquid crystal formation. Guided by mathematical modeling, we identified the primary components of the liquid core to be HSP70 family chaperones, whose adenosine triphosphate (ATP)-dependent activity maintained the liquidity of shells and cores. In vivo proteasome inhibition within neurons, to mimic aging-related reduction of proteasome activity, induced TDP-43-containing anisosomes. These structures converted to aggregates when ATP levels were reduced. Thus, acetylation, HSP70, and proteasome activities regulate TDP-43 phase separation and conversion into a gel or solid phase.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8598b09mTest

المؤلفون: Selbmann, Laura, Benkő, Zsigmond, Coleine, Claudia, de Hoog, Sybren, Donati, Claudio, Druzhinina, Irina, Emri, Tamás, Ettinger, Cassie L, Gladfelter, Amy S, Gorbushina, Anna A, Grigoriev, Igor V, Grube, Martin, Gunde-Cimerman, Nina, Karányi, Zsolt Ákos, Kocsis, Beatrix, Kubressoian, Tania, Miklós, Ida, Miskei, Márton, Muggia, Lucia, Northen, Trent, Novak-Babič, Monika, Pennacchio, Christa, Pfliegler, Walter P, Pòcsi, Istvàn, Prigione, Valeria, Riquelme, Meritxell, Segata, Nicola, Schumacher, Julia, Shelest, Ekaterina, Sterflinger, Katja, Tesei, Donatella, U'Ren, Jana M, Varese, Giovanna C, Vázquez-Campos, Xabier, Vicente, Vania A, Souza, Emanuel M, Zalar, Polona, Walker, Allison K, Stajich, Jason E

المصدر: Life (Basel, Switzerland). 10(12)

مصطلحات موضوعية: Dothideomycetes, Eurotiomycetes, adaptation, black fungi, extremophiles, genomics, metabolomics, secondary metabolites, stress conditions, transcriptomics

الوصف: The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to stresses including UV- and ionizing-radiation, heat and desiccation, toxic metals, and organic pollutants. Consequently, they are amongst the most stunning extremophiles and poly-extreme-tolerant organisms on Earth. Even though ca. 60 black fungal genomes have been sequenced to date, [mostly in the family Herpotrichiellaceae (Eurotiomycetes)], the class Dothideomycetes that hosts the largest majority of extremophiles has only been sparsely sampled. By sequencing up to 92 species that will become reference genomes, the "Shed light in The daRk lineagES of the fungal tree of life" (STRES) project will cover a broad collection of black fungal diversity spread throughout the Fungal Tree of Life. Interestingly, the STRES project will focus on mostly unsampled genera that display different ecologies and life-styles (e.g., ant- and lichen-associated fungi, rock-inhabiting fungi, etc.). With a resequencing strategy of 10- to 15-fold depth coverage of up to ~550 strains, numerous new reference genomes will be established. To identify metabolites and functional processes, these new genomic resources will be enriched with metabolomics analyses coupled with transcriptomics experiments on selected species under various stress conditions (salinity, dryness, UV radiation, oligotrophy). The data acquired will serve as a reference and foundation for establishing an encyclopedic database for fungal metagenomics as well as the biology, evolution, and ecology of the fungi in extreme environments.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/71p5t489Test

المؤلفون: Amend, Anthony, Burgaud, Gaetan, Cunliffe, Michael, Edgcomb, Virginia P, Ettinger, Cassandra L, Gutiérrez, MH, Heitman, Joseph, Hom, Erik FY, Ianiri, Giuseppe, Jones, Adam C, Kagami, Maiko, Picard, Kathryn T, Quandt, C Alisha, Raghukumar, Seshagiri, Riquelme, Mertixell, Stajich, Jason, Vargas-Muñiz, José, Walker, Allison K, Yarden, Oded, Gladfelter, Amy S

المصدر: mBio. 10(2)

مصطلحات موضوعية: Life Below Water, Aquatic Organisms, Biodiversity, Fungi, Geologic Sediments, Seawater, mycology, chytrid, marine fungi, marine microbiology, Microbiology

الوصف: Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer than 10% of fungi have been identified so far. To date, a relatively small percentage of described species are associated with marine environments, with ∼1,100 species retrieved exclusively from the marine environment. Nevertheless, fungi have been found in nearly every marine habitat explored, from the surface of the ocean to kilometers below ocean sediments. Fungi are hypothesized to contribute to phytoplankton population cycles and the biological carbon pump and are active in the chemistry of marine sediments. Many fungi have been identified as commensals or pathogens of marine animals (e.g., corals and sponges), plants, and algae. Despite their varied roles, remarkably little is known about the diversity of this major branch of eukaryotic life in marine ecosystems or their ecological functions. This perspective emerges from a Marine Fungi Workshop held in May 2018 at the Marine Biological Laboratory in Woods Hole, MA. We present the state of knowledge as well as the multitude of open questions regarding the diversity and function of fungi in the marine biosphere and geochemical cycles.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8m70c96nTest

المؤلفون: Li, Hongda, Saucedo-Cuevas, Laura, Yuan, Ling, Ross, Danica, Johansen, Anide, Sands, Daniel, Stanley, Valentina, Guemez-Gamboa, Alicia, Gregor, Anne, Evans, Todd, Chen, Shuibing, Tan, Lei, Molina, Henrik, Sheets, Nicholas, Shiryaev, Sergey A, Terskikh, Alexey V, Gladfelter, Amy S, Shresta, Sujan, Xu, Zhiheng, Gleeson, Joseph G

المصدر: Neuron. 101(6)

مصطلحات موضوعية: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Stem Cell Research, Infectious Diseases, Good Health and Well Being, Apoptosis, Cytokinesis, Cytoskeleton, HEK293 Cells, HeLa Cells, Humans, Mitosis, Neural Stem Cells, Neurogenesis, RNA Helicases, Septins, Serine Endopeptidases, Viral Nonstructural Proteins, Zika Virus, Hela Cells, Zika, activated caspase, cytokinesis, microcephaly, protease, septin, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology

الوصف: Zika virus (ZIKV) targets neural progenitor cells in the brain, attenuates cell proliferation, and leads to cell death. Here, we describe a role for the ZIKV protease NS2B-NS3 heterodimer in mediating neurotoxicity through cleavage of a host protein required for neurogenesis. Similar to ZIKV infection, NS2B-NS3 expression led to cytokinesis defects and cell death in a protease activity-dependent fashion. Among binding partners, NS2B-NS3 cleaved Septin-2, a cytoskeletal factor involved in cytokinesis. Cleavage of Septin-2 occurred at residue 306 and forced expression of a non-cleavable Septin-2 restored cytokinesis, suggesting a direct mechanism of ZIKV-induced neural toxicity. VIDEO ABSTRACT.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9tf0824pTest

المؤلفون: Lin, Andrew Z., Ruff, Kiersten M., Dar, Furqan, Jalihal, Ameya, King, Matthew R., Lalmansingh, Jared M., Posey, Ammon E., Erkamp, Nadia A., Seim, Ian, Gladfelter, Amy S., Pappu, Rohit V.

المساهمون: United States Department of Defense | United States Air Force | AFMC | Air Force Office of Scientific Research, Foundation for the National Institutes of Health

المصدر: Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, in Ashbya gossypii , the RNA-binding protein Whi3 forms distinct condensates with different RNA molecules. Using criteria derived from a physical framework for explaining how compositionally distinct condensates can form spontaneously via thermodynamic considerations, we find that condensates in vitro form mainly via heterotypic interactions in binary mixtures of Whi3 and RNA. However, within these condensates, RNA molecules become dynamically arrested. As a result, in ternary systems, simultaneous additions of Whi3 and pairs of distinct RNA molecules lead to well-mixed condensates, whereas delayed addition of an RNA component results in compositional distinctness. Therefore, compositional identities of condensates can be achieved via dynamical control, being driven, at least partially, by the dynamical arrest of RNA molecules. Finally, we show that synchronizing the production of different RNAs leads to more well-mixed, as opposed to compositionally distinct condensates in vivo.

الإتاحة: https://doi.org/10.1038/s41467-023-43489-4Test
https://www.nature.com/articles/s41467-023-43489-4.pdfTest
https://www.nature.com/articles/s41467-023-43489-4Test

المؤلفون: Cannon, Kevin S., Vargas-Muniz, Jose M., Billington, Neil, Seim, Ian, Ekena, Joanne, Sellers, James R., Gladfelter, Amy. S.

المساهمون: National Science Foundation, Division of Molecular and Cellular Biosciences, Howard Hughes Medical Institute, National Institute of General Medical Sciences, National Institutes of Health

المصدر: Journal of Cell Biology ; volume 222, issue 3 ; ISSN 0021-9525 1540-8140

الوصف: Septins are a family of conserved filament-forming proteins that function in multiple cellular processes. The number of septin genes within an organism varies, and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear if different combinations of septin proteins in complex alter the polymers’ biophysical properties. We report that a duplication event within the CDC11 locus in Ashbya gossypii gave rise to two similar but distinct Cdc11 proteins: Cdc11a and Cdc1b. CDC11b transcription is developmentally regulated, producing different amounts of Cdc11a- and Cdc11b-complexes in the lifecycle of Ashbya gossypii. Deletion of either gene results in distinct cell polarity defects, suggesting non-overlapping functions. Cdc11a and Cdc11b complexes have differences in filament length and membrane-binding ability. Thus, septin subunit composition has functional consequences on filament properties and cell morphogenesis. Small sequence differences elicit distinct biophysical properties and cell functions of septins, illuminating how gene duplication could be a driving force for septin gene expansions seen throughout the tree of life.

الإتاحة: https://doi.org/10.1083/jcb.202204063Test

المؤلفون: Snead, Wilton T., Shrinivas, Krishna, Babaki, Danial, Weeks, Kevin M., Gladfelter, Amy S.

المصدر: Biophysical Journal ; volume 122, issue 3, page 67a ; ISSN 0006-3495

مصطلحات موضوعية: Biophysics

الإتاحة: https://doi.org/10.1016/j.bpj.2022.11.571Test
https://api.elsevier.com/content/article/PII:S0006349522014874?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0006349522014874?httpAccept=text/plainTest

المؤلفون: Pappu, Rohit V., Lin, Andrew Z., Ruff, Kiersten M., Jalihal, Ameya P., Dar, Furqan, Posey, Ammon E., King, Matthew R., Lalmansingh, Jared M., Gladfelter, Amy S.

المصدر: Biophysical Journal ; volume 122, issue 3, page 443a ; ISSN 0006-3495

مصطلحات موضوعية: Biophysics

الإتاحة: https://doi.org/10.1016/j.bpj.2022.11.2390Test
https://api.elsevier.com/content/article/PII:S0006349522033069?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0006349522033069?httpAccept=text/plainTest

المؤلفون: Mayer, Alexander J., Roper, Marcus, Gladfelter, Amy S., McLaughlin, Grace

المصدر: Biophysical Journal ; volume 122, issue 3, page 415a-416a ; ISSN 0006-3495

مصطلحات موضوعية: Biophysics

الإتاحة: https://doi.org/10.1016/j.bpj.2022.11.2256Test
https://api.elsevier.com/content/article/PII:S0006349522031721?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0006349522031721?httpAccept=text/plainTest

المؤلفون: Seim, Ian, Graham, Austin J., Mathijssen, Arnold, Gladfelter, Amy S.

المصدر: Biophysical Journal ; volume 122, issue 3, page 295a ; ISSN 0006-3495

مصطلحات موضوعية: Biophysics

الإتاحة: https://doi.org/10.1016/j.bpj.2022.11.1670Test
https://api.elsevier.com/content/article/PII:S0006349522025863?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0006349522025863?httpAccept=text/plainTest