Proteasomes are multisubunit proteases that play a critical role in maintaining cellular function through the selective degradation of ubiquitinated proteins. When 3 additional β subunits, expression of which is induced by IFN-γ, are substituted for their constitutively expressed counterparts, the structure is converted to an immunoproteasome. However, the underlying roles of immunoproteasomes in human diseases are poorly understood. Using exome analysis, we found a homozygous missense mutation (G197V) in immunoproteasome subunit, β type 8 (PSMB8), which encodes one of the β subunits induced by IFN-γ in patients from 2 consanguineous families. Patients bearing this mutation suffered from autoinflammatory responses that included recurrent fever and nodular erythema together with lipodystrophy. This mutation increased assembly intermediates of immunoproteasomes, resulting in decreased proteasome function and ubiquitin-coupled protein accumulation in the patient's tissues. In the patient's skin and B cells, IL-6 was highly expressed, and there was reduced expression of PSMB8. Downregulation of PSMB8 inhibited the differentiation of murine and human adipocytes in vitro, and injection of siRNA against Psmb8 in mouse skin reduced adipocyte tissue volume. These findings identify PSMB8 as an essential component and regulator not only of inflammation, but also of adipocyte differentiation, and indicate that immunoproteasomes have pleiotropic functions in maintaining the homeostasis of a variety of cell types.
Expanded polyglutamine (polyQ) repeats cause neurodegenerative disorders, but their cytotoxic structures remain to be elucidated. Although soluble polyQ oligomers have been proposed as a cytotoxic structure, the cytotoxicity of soluble polyQ oligomers, not inclusion bodies (IBs), has not been proven in living cells. To clarify the cytotoxicity of soluble polyQ oligomers, we carried our fluorescence resonance energy transfer (FRET) confocal microscopy and distinguished oligomers from monomers and IBs in a single living cell. FRET signals were detected when donor and acceptor fluorescent proteins were attached to the same side, not the opposite side, of polyQ repeats, which agrees with a parallel beta-sheet or a head-to-tail cylindrical beta-sheet model. These FRET signals disappeared in semi-intact cells, indicating that these polyQ oligomers are soluble. PolyQ monomers assembled into soluble oligomers in a length-dependent manner, which was followed by the formation of IBs. Notably, survival assay of neuronally differentiated cells revealed that cells with soluble oligomers died faster than those with IBs or monomers. These results indicate that a length-dependent formation of oligomers is an essential mechanism underlying neurodegeneration in polyQ-mediated disorders.
mol/cell per d with bicarbonate. Neither carbon assimilation nor growth was evident in response to methane. The atomic ratios between nitrogen incorporated from ammonium and the total cellular nitrogen consistently exceeded the ratios of carbon, suggesting that subseafloor microbes preferentially require nitrogen assimilation for the recovery in vitro. Our results showed that the most deeply buried subseafloor sedimentary microbes maintain potentials for metabolic activities and that growth is generally limited by energy but not by the availability of C and N compounds.
The Challenger Deep is the deepest ocean on Earth. The present study investigated microbial community structures and geochemical cycles associated with the trench bottom sediments of the Challenger Deep, the Mariana Trench. The SSU rRNA gene communities found in trench bottom sediments were dominated by the bacteria Chloroflexi (SAR202 and other lineages), Bacteroidetes, Planctomycetes, “Ca. Marinimicrobia” (SAR406), and Gemmatimonadetes and by the archaeal α subgroup of MGI Thaumarchaeota and “Ca. Woesearchaeota” (Deep-sea Hydrothermal Vent Euryarchaeotic Group 6). The SSU rRNA gene sequencing analysis indicated that the dominant populations of the thaumarchaeal α group in hadal water and sediments were similar to each other at the species or genus level. In addition, the co-occurrence of nitrification and denitrification was revealed by the combination of pore water geochemical analyses and quantitative PCR for nitrifiers.
There has been much progress in understanding the nitrogen cycle in oceanic waters including the recent identification of ammonia-oxidizing archaea and anaerobic ammonia oxidizing (anammox) bacteria, and in the comprehensive estimation in abundance and activity of these microbial populations. However, compared with the nitrogen cycle in oceanic waters, there are fewer studies concerning the oceanic benthic nitrogen cycle. To further elucidate the dynamic nitrogen cycle in deep-sea sediments, a sediment core obtained from the Ogasawara Trench at a water depth of 9760 m was analysed in this study. The profiles obtained for the pore-water chemistry, and nitrogen and oxygen stable isotopic compositions of pore-water nitrate in the hadopelagic sediments could not be explained by the depth segregation of nitrifiers and nitrate reducers, suggesting the co-occurrence of nitrification and nitrate reduction in the shallowest nitrate reduction zone. The abundance of SSU rRNA and functional genes related to nitrification and denitrification are consistent with the co-occurrence of nitrification and nitrate reduction observed in the geochemical analyses. This study presents the first example of cooperation between aerobic and anaerobic nitrogen metabolism in the deep-sea sedimentary environments.
Hadal trench bottom (>6000 m below sea level) sediments harbor higher microbial cell abundance compared with adjacent abyssal plain sediments. This is supported by the accumulation of sedimentary organic matter (OM), facilitated by trench topography. However, the distribution of benthic microbes in different trench systems has not been well explored yet. Here, we carried out small subunit ribosomal RNA gene tag sequencing for 92 sediment subsamples of seven abyssal and seven hadal sediment cores collected from three trench regions in the northwest Pacific Ocean: the Japan, Izu-Ogasawara, and Mariana Trenches. Tag-sequencing analyses showed specific distribution patterns of several phyla associated with oxygen and nitrate. The community structure was distinct between abyssal and hadal sediments, following geographic locations and factors represented by sediment depth. Co-occurrence network revealed six potential prokaryotic consortia that covaried across regions. Our results further support that the OM cycle is driven by hadal currents and/or rapid burial shapes microbial community structures at trench bottom sites, in addition to vertical deposition from the surface ocean. Our trans-trench analysis highlights intra-and inter-trench distributions of microbial assemblages and geochemistry in surface seafloor sediments, providing novel insights into ultradeep-sea microbial ecology, one of the last frontiers on our planet.
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