Observation of time quasicrystal and its transition to superfluid time crystal

We report experimental realization of a quantum time quasicrystal, and its transformation to a quantum time crystal. We study Bose-Einstein condensation of magnons, associated with coherent spin precession, created in a flexible trap in superfluid $^3$He-B. Under a periodic drive with an oscillating magnetic field, the coherent spin precession is stabilized at a frequency smaller than that of the drive, demonstrating spontaneous breaking of discrete time translation symmetry. The induced precession frequency is incommensurate with the drive, and hence the obtained state is a time quasicrystal. When the drive is turned off, the self-sustained coherent precession lives a macroscopically-long time, now representing a time crystal with broken symmetry with respect to continuous time translations. Additionally, the magnon condensate manifests spin superfluidity, justifying calling the obtained state a time supersolid or a time super-crystal

Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling

published_or_final_versio

Inhibition of TLR4 Signaling by TRAM-Derived Decoy Peptides In Vitro and In Vivo

Abstract Toll/IL-1R (TIR) domain-containing adapter-inducing IFN-β (TRIF)–related adapter molecule (TRAM) serves as a bridging adapter that enables recruitment of TRIF to activated TLR4 and thereby mediates the induction of TRIF-dependent cytokines. A library of cell-permeating decoy peptides derived from TRAM TIR domain has been screened for the ability of individual peptides to inhibit TLR4 signaling in primary murine macrophages. Peptides derived from TRAM TIR BB loop (TM4) and C helix (TM6) inhibited the LPS-induced activation of MyD88-dependent and TRIF-dependent cytokines, as well as MAPK activation. TM4 and TM6 did not block macrophage activation induced by TLR2, TLR9, or retinoic acid–inducible gene 1–like receptor agonists. Both TM4 and TM6 blocked coimmunoprecipitation of TRAM and TLR4 ectopically expressed in HEK293T cells. Both peptides also blocked the LPS-induced recruitment of MyD88 to TLR4 in primary murine macrophages. In vivo examination of TRAM-derived peptides demonstrated that all peptides that were inhibitory in vitro profoundly suppressed systemic inflammatory response elicited in mice by a sublethal LPS dose, and protected mice against a lethal LPS challenge. This research identifies novel TLR inhibitors effective in vitro and in vivo and validates the approach taken in this study as a rational way for development of signaling inhibitors and lead therapeutics.</jats:p

Proinflammatory cytokine production by adherent donor blood cells stimulated by soluble LPS and phagocyted bacteria

Specific stimulation of receptors of the innate immune system by their purified ligands is commonly used in basic studies of inflammation and in the development of anti-inflammatory drugs. Based on location, receptors of the innate immunity can be classified into two groups: i) cell plasma membrane and on membranes of endosomes (Toll-like receptors (TLRs) and C-type lectin receptors), and recognizing the presence of pathogens in the extracellular space; ii) cytoplasmic sensors playing a special role in the recognition of intracellular pathogens (NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), bacterial DNA sensor cGAS, and Aim2 (absent in melanoma 2). Many experimental models of inflammation use bacterial lipopolysaccharides (LPSs) or other purified microbial molecules to simulate the innate immune response to microbes. In the present study, the response of human blood leukocytes to stimulation with soluble, highly purified LPS from gram-negative bacteria was compared with that induced by formalin-fixed, corpuscular E. coli. The data obtained demonstrate that LPS and bacteria induce similar levels of TNF and IL-6 by plastic-adherent leukocytes, whereas neither LPS nor whole bacteria induce a measurable IFNγ production. The LPS- and bacteria-induced cytokine production, however, drastically differed in the sensitivity to a broad-spectrum TLR inhibitor, peptide 5R667. The LPS-stimulated human leukocyte cytokine production, as expected, was highly sensitive to inhibition by the peptide, whereas production stimulated by corpuscular bacteria was not. The TLR-blocking peptide did not affect the ability of blood leukocytes to phagocytose E. coli as shown by flow cytometry data obtained using FITC-stained fixed bacteria. Because peptide 5R667 blocks several TLRs, including TLR4, TLR5, and TLR9, the differential sensitivity of LPS- and bacteria-induced cytokine production to 5R667 suggests that the intracellular pathogen sensors, most likely NOD1 and/or NOD2, essentially contribute to the bacteria-induced cytokine induction. These results show that LPS and phagocyted bacteria induce cytokine production via different mechanisms and also suggest that the models with corpuscular bacteria for simulating bacterially induced inflammation complement the models that using soluble TLR ligands; therefore, both models should be applied to properly reflect anti-bacterial immune response

Diversity of “Ca. Micrarchaeota” in two distinct types of acidic environments and their associations with Thermoplasmatales

&ldquo;Candidatus Micrarchaeota&rdquo; are widely distributed in acidic environments; however, their cultivability and our understanding of their interactions with potential hosts are very limited. Their habitats were so far attributed with acidic sites, soils, peats, freshwater systems, and hypersaline mats. Using cultivation and culture-independent approaches (16S rRNA gene clonal libraries, high-throughput amplicon sequencing of V3-V4 region of 16S rRNA genes), we surveyed the occurrence of these archaea in geothermal areas on Kamchatka Peninsula and Kunashir Island and assessed their taxonomic diversity in relation with another type of low-pH environment, acid mine drainage stream (Wales, UK). We detected &ldquo;Ca. Micrarchaeota&rdquo; in thermophilic heterotrophic enrichment cultures of Kunashir and Kamchatka that appeared as two different phylotypes, namely &ldquo;Ca. Mancarchaeum acidiphilum&rdquo;-, and ARMAN-2-related, alongside their potential hosts, Cuniculiplasma spp. and other Thermoplasmatales archaea without defined taxonomic position. These clusters of &ldquo;Ca. Micrarchaeota&rdquo; together with three other groups were also present in mesophilic acid mine drainage community. Present work expands our knowledge on the diversity of &ldquo;Ca. Micrarchaeota&rdquo; in thermophilic and mesophilic acidic environments, suggests cultivability patterns of acidophilic archaea and establishes potential links between low-abundance species of thermophilic &ldquo;Ca. Micrarchaeota&rdquo; and certain Thermoplasmatales, such as Cuniculiplasma spp. in situ

Evaluation of versions of electric power grid repair schemes from the results of structural reliability calculations

A procedure for processing repair claims using the results of an estimate of the structural reliability of the electric grid, the results of the approval of algorithms using the example of a test model, and the principles for producing short-term charts of the repairs of electric-grid equipment, is presented. © 2013 Springer Science+Business Media New York

Sulfur Respiration in a Group of Facultatively Anaerobic Natronoarchaea Ubiquitous in Hypersaline Soda Lakes

The ubiquity of strictly anaerobic sulfur-respiring haloarchaea in hypersaline systems with circumneutral pH has shaken a traditional concept of this group as predominantly aerobic heterotrophs. Here, we demonstrated that this functional group of haloarchaea also has its representatives in hypersaline alkaline lakes. Sediments from various hypersaline soda lakes showed high activity of sulfur reduction only partially inhibited by antibiotics. Eight pure cultures of sulfur-reducing natronoarchaea were isolated from such sediments using formate and butyrate as electron donors and sulfur as an electron acceptor. Unlike strict anaerobic haloarchaea, these novel sulfur-reducing natronoarchaea are facultative anaerobes, whose metabolic capabilities were inferred from cultivation experiments and genomic/proteomic reconstruction. While sharing many physiological traits with strict anaerobic haloarchaea, following metabolic distinctions make these new organisms be successful in both anoxic and aerobic habitats: the recruiting of heme-copper quinol oxidases as terminal electron sink in aerobic respiratory chain and the utilization of formate, hydrogen or short-chain fatty acids as electron donors during anaerobic growth with elemental sulfur. Obtained results significantly advance the emerging concept of halo(natrono)archaea as important players in the anaerobic sulfur and carbon cycling in various salt-saturated habitats.BT/Environmental Biotechnolog

Archaea dominate the microbial community in an ecosystem with low-to-moderate temperature and extreme acidity

[Background] The current view suggests that in low-temperature acidic environments, archaea are significantly less abundant than bacteria. Thus, this study of the microbiome of Parys Mountain (Anglesey, UK) sheds light on the generality of this current assumption. Parys Mountain is a historically important copper mine and its acid mine drainage (AMD) water streams are characterised by constant moderate temperatures (8–18 °C), extremely low pH (1.7) and high concentrations of soluble iron and other metal cations.[Results] Metagenomic and SSU rRNA amplicon sequencing of DNA from Parys Mountain revealed a significant proportion of archaea affiliated with Euryarchaeota, which accounted for ca. 67% of the community. Within this phylum, potentially new clades of Thermoplasmata were overrepresented (58%), with the most predominant group being “E-plasma”, alongside low-abundant Cuniculiplasmataceae, ‘Ca. Micrarchaeota’ and ‘Terrestrial Miscellaneous Euryarchaeal Group’ (TMEG) archaea, which were phylogenetically close to Methanomassilicoccales and clustered with counterparts from acidic/moderately acidic settings. In the sediment, archaea and Thermoplasmata contributed the highest numbers in V3-V4 amplicon reads, in contrast with the water body community, where Proteobacteria, Nitrospirae, Acidobacteria and Actinobacteria outnumbered archaea. Cultivation efforts revealed the abundance of archaeal sequences closely related to Cuniculiplasma divulgatum in an enrichment culture established from the filterable fraction of the water sample. Enrichment cultures with unfiltered samples showed the presence of Ferrimicrobium acidiphilum, C. divulgatum, ‘Ca. Mancarchaeum acidiphilum Mia14’, ‘Ca. Micrarchaeota’-related and diverse minor (< 2%) bacterial metagenomic reads.[Conclusion] Contrary to expectation, our study showed a high abundance of archaea in this extremely acidic mine-impacted environment. Further, archaeal populations were dominated by one particular group, suggesting that they are functionally important. The prevalence of archaea over bacteria in these microbiomes and their spatial distribution patterns represents a novel and important advance in our understanding of acidophile ecology. We also demonstrated a procedure for the specific enrichment of cell wall-deficient members of the archaeal component of this community, although the large fraction of archaeal taxa remained unculturable. Lastly, we identified a separate clustering of globally occurring acidophilic members of TMEG that collectively belong to a distinct order within Thermoplasmata with yet unclear functional roles in the ecosystem.The work of OVG, PNG and SVT was supported by the Royal Society UK-Russia Exchange Grant #IE 160224 (RFBR 16-54-10072 КО project). OVG and PNG acknowledge ERA Net IB2 Project MetaCat through UK Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/M029085/1 and the support of the Centre of Environmental Biotechnology Project funded by the European Regional Development Fund (ERDF) through the Welsh Government. RB and PNG acknowledge the support of the Supercomputing Wales project, which is part-funded by the European Regional Development Fund (ERDF) via the Welsh Government. The work of AAK and IVK was supported by the Russian Science Foundation grant # 18-44-04024. MF acknowledges grants PCIN-2014-107 (within ERA NET IB2 grant ERA-IB-14-030—MetaCat), PCIN-2017-078 (within the Marine Biotechnology ERA-NET (ERA-MBT) funded under the European Commission’s Seventh Framework Programme, 2013-2017, Grant agreement 604814), BIO2014-54494-R and BIO2017-85522-R from the Spanish Ministry of Economy and Competitiveness