Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in ...atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr-/-) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment of atherosclerosis.
Biological methane formation starts with a challenging adenosine triphosphate (ATP)-independent carbon dioxide (CO₂) fixation process. We explored this enzymatic process by solving the x-ray crystal ...structure of formyl-methanofuran dehydrogenase, determined here as Fwd(ABCDFG)₂ and Fwd(ABCDFG)₄ complexes, from Methanothermobacter wolfeii. The latter 800-kilodalton apparatus consists of four peripheral catalytic sections and an electron-supplying core with 46 electronically coupled 4Fe-4S clusters. Catalysis is separately performed by subunits FwdBD (FwdB and FwdD), which are related to tungsten-containing formate dehydrogenase, and subunit FwdA, a binuclear metal center carrying amidohydrolase. CO₂ is first reduced to formate in FwdBD, which then diffuses through a 43-angstrom-long tunnel to FwdA, where it condenses with methanofuran to formyl-methanofuran. The arrangement of 4Fe-4S clusters functions as an electron relay but potentially also couples the four tungstopterin active sites over 206 angstroms.
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are ...chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding-dependent role that ensures adequate repair of common replication errors.
Between 1999 and 2006, a plateau interrupted the otherwise continuous increase of atmospheric methane concentration CH₄ since preindustrial times. Causes could be sink variability or a temporary ...reduction in industrial or climate-sensitive sources. We reconstructed the global history of CH₄ and its stable carbon isotopes from ice cores, archived air, and a global network of monitoring stations. A box-model analysis suggests that diminishing thermogenic emissions, probably from the fossil-fuel industry, and/or variations in the hydroxyl CH₄ sink caused the CH₄ plateau. Thermogenic emissions did not resume to cause the renewed CH₄ rise after 2006, which contradicts emission inventories. Post-2006 source increases are predominantly biogenic, outside the Arctic, and arguably more consistent with agriculture than wetlands. If so, mitigating CH₄ emissions must be balanced with the need for food production.
Evidence for hydrodynamic electron flow in PdCoO Moll, Philip J. W.; Kushwaha, Pallavi; Nandi, Nabhanila ...
Science (American Association for the Advancement of Science),
03/2016, Volume:
351, Issue:
6277
Journal Article
Peer reviewed
Electron transport is conventionally determined by the momentum-relaxing scattering of electrons by the host solid and its excitations. Hydrodynamic fluid flow through channels, in contrast, is ...determined partly by the viscosity of the fluid, which is governed by momentum-conserving internal collisions. A long-standing question in the physics of solids has been whether the viscosity of the electron fluid plays an observable role in determining the resistance. We report experimental evidence that the resistance of restricted channels of the ultrapure two-dimensional metal palladium cobaltate (PdCoO₂) has a large viscous contribution. Comparison with theory allows an estimate of the electronic viscosity in the range between 6 × 10⁻³ kg m⁻¹ s⁻¹ and 3 × 10⁻⁴ kg m⁻¹ s⁻¹, versus 1 × 10⁻³ kg m⁻¹ s⁻¹ for water at room temperature.
The smooth disappearance of antiferromagnetic order in strongly correlated metals commonly furnishes the development of unconventional superconductivity. The canonical heavy-electron compound ...YbRh₂Si₂ seems to represent an apparent exception from this quantum critical paradigm in that it is not a superconductor at temperature T ≥ 10 millikelvin (mK). Here we report magnetic and calorimetric measurements on YbRh₂Si₂, down to temperatures as low as T ≈ 1 mK. The data reveal the development of nuclear antiferromagnetic order slightly above 2 mK and of heavy-electron superconductivity almost concomitantly with this order. Our results demonstrate that superconductivity in the vicinity of quantum criticality is a general phenomenon.
The Zeeman effect, which is usually detrimental to superconductivity, can be strongly protective when an effective Zeeman field from intrinsic spin-orbit coupling locks the spins of Cooper pairs in a ...direction orthogonal to an external magnetic field. We performed magnetotransport experiments with ionic-gated molybdenum disulfide transistors, in which gating prepared individual superconducting states with different carrier dopings, and measured an in-plane critical field Bc2 far beyond the Pauli paramagnetic limit, consistent with Zeeman-protected superconductivity. The gating-enhanced Bc2 is more than an order of magnitude larger than it is in the bulk superconducting phases, where the effective Zeeman field is weakened by interlayer coupling. Our study provides experimental evidence of an Ising superconductor, in which spins of the pairing electrons are strongly pinned by an effective Zeeman field.
Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding ...of a small five-helix protein domain–the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK–in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains.
Near-unity photoluminescence quantum yield in MoS Amani, Matin; Lien, Der-Hsien; Kiriya, Daisuke ...
Science (American Association for the Advancement of Science),
11/2015, Volume:
350, Issue:
6264
Journal Article
Peer reviewed
Two-dimensional (2D) transition metal dichalcogenides have emerged as a promising material system for optoelectronic applications, but their primary figure of merit, the room-temperature ...photoluminescence quantum yield (QY), is extremely low. The prototypical 2D material molybdenum disulfide (MoS₂) is reported to have a maximum QY of 0.6%, which indicates a considerable defect density. Here we report on an air-stable, solution-based chemical treatment by an organic superacid, which uniformly enhances the photoluminescence and minority carrier lifetime of MoS₂ monolayers by more than two orders of magnitude. The treatment eliminates defect-mediated nonradiative recombination, thus resulting in a final QY of more than 95%, with a longest-observed lifetime of 10.8 0.6 nanoseconds. Our ability to obtain optoelectronic monolayers with near-perfect properties opens the door for the development of highly efficient light-emitting diodes, lasers, and solar cells based on 2D materials.
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