Even though the terahertz spectrum is well suited for chemical identification, material characterization, biological sensing and medical imaging, practical development of these applications has been ...hindered by attributes of existing terahertz optoelectronics. Here we demonstrate that the use of plasmonic contact electrodes can significantly mitigate the low-quantum efficiency performance of photoconductive terahertz optoelectronics. The use of plasmonic contact electrodes offers nanoscale carrier transport path lengths for the majority of photocarriers, increasing the number of collected photocarriers in a subpicosecond timescale and, thus, enhancing the optical-to-terahertz conversion efficiency of photoconductive terahertz emitters and the detection sensitivity of photoconductive terahertz detectors. We experimentally demonstrate 50 times higher terahertz radiation powers from a plasmonic photoconductive emitter in comparison with a similar photoconductive emitter with non-plasmonic contact electrodes, as well as 30 times higher terahertz detection sensitivities from a plasmonic photoconductive detector in comparison with a similar photoconductive detector with non-plasmonic contact electrodes.
Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain ...unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)- dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.
On Jan. 15, 2022, the Hunga Tonga-Hunga Ha’apai eruption injected SO2 and H2O into the 31 middle stratosphere. The eruption produced a persistent mid-stratospheric sulfate aerosol and H2O layer ...mostly confined to Southern Hemisphere (SH) tropics (Eq. to 30°S). These layers are still present in the tropics 5 ½ months after the eruption. The SH tropical confinement is simulated using a trajectory model. Measurements following the eruption show that the H2O layer is slowly rising while the aerosol layer is descending. The H2O layer’s upward movement is consistent with the residual vertical velocity. Gravitationally settling explains the descent of the aerosol layer. A -4K temperature anomaly coincident with the H2O enhancement is observed and is caused by thermal adjustment to the additional H2O IR cooling. A simple model of volcanic water injection at the time of the eruption simulates the observed vertical distribution H2O.
Cellular processes often depend on stable physical associations between proteins. Despite recent progress, knowledge of the composition of human protein complexes remains limited. To close this gap, ...we applied an integrative global proteomic profiling approach, based on chromatographic separation of cultured human cell extracts into more than one thousand biochemical fractions that were subsequently analyzed by quantitative tandem mass spectrometry, to systematically identify a network of 13,993 high-confidence physical interactions among 3,006 stably associated soluble human proteins. Most of the 622 putative protein complexes we report are linked to core biological processes and encompass both candidate disease genes and unannotated proteins to inform on mechanism. Strikingly, whereas larger multiprotein assemblies tend to be more extensively annotated and evolutionarily conserved, human protein complexes with five or fewer subunits are far more likely to be functionally unannotated or restricted to vertebrates, suggesting more recent functional innovations.
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► Proteomic profiling identifies 13,993 physical interactions among 3,006 proteins ► The interactions lead to a map of 622 complexes, many of which are highly conserved ► The map reveals many unexpected biological and disease associations
An unbiased, integrative approach reveals hundreds of new protein complexes and implicates unexpected proteins as components of known multisubunit assemblies. Evolutionary analyses highlight vertebrate-specific assemblies, whereas other complexes appear highly conserved.
Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC ...cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC.
Electrically insulating objects gain a net electrical charge when brought in and out of contact. This phenomenontriboelectricityinvolves the flow of charged species, but conclusively establishing ...their nature has proven extremely difficult. Here, we demonstrate an almost linear relationship between a plastic sample’s net negative charge and the amount of solution metal ions discharged to metallic particles with a coefficient of proportionality linked to its electron affinity (stability of anionic fragments). The maximum magnitude of reductive redox work is also material dependent: metallic particles grow to a larger extent over charged dielectrics that yield stable cationic fragments (smaller ionization energy). Importantly, the extent to which the sample can act as electron source greatly exceeds the net charging measured in a Faraday pail/electrometer set up, which brings direct evidence of triboeletricity being a mosaic of positive and negative charges rather than a homogeneous ensemble and defines for the first time their quantitative scope in electrochemistry.
We have discovered a 300 kpc-wide giant Lyman-
α
(Ly
α
) nebula centered on the massive galaxy group RO-1001 at
z
= 2.91 in the Cosmic Evolution Survey field. Keck Cosmic Web Imager observations ...reveal three cold gas filaments converging into the center of the potential well of its ∼4 × 10
13
M
⊙
dark matter halo, hosting 1200
M
⊙
yr
−1
of star formation as probed by Atacama Large Millimeter Array and NOrthern Extended Millimeter Array observations. The nebula morphological and kinematics properties and the prevalence of blueshifted components in the Ly
α
spectra are consistent with a scenario of gas accretion. The upper limits on active galactic nuclei activity and overall energetics favor gravity as the primary Ly
α
powering source and infall as the main source of gas flows to the system. Although interpretational difficulties remain, with outflows and likely also photoionization with ensuing recombination still playing a role, this finding provides arguably an ideal environment to quantitatively test models of cold gas accretion and galaxy feeding inside an actively star-forming massive halo at high redshift.
The surfaces of metal oxides often are reconstructed with a geometry and composition that is considerably different from a simple termination of the bulk. Such structures can also be viewed as ...ultrathin films, epitaxed on a substrate. Here, the reconstructions of the SrTiO3 (110) surface are studied combining scanning tunneling microscopy (STM), transmission electron diffraction, and X-ray absorption spectroscopy (XAS), and analyzed with density functional theory calculations. Whereas SrTiO3 (110) invariably terminates with an overlayer of titania, with increasing density its structure switches from n × 1 to 2 × n. At the same time the coordination of the Ti atoms changes from a network of corner-sharing tetrahedra to a double layer of edge-shared octahedra with bridging units of octahedrally coordinated strontium. This transition from the n × 1 to 2 × n reconstructions is a transition from a pseudomorphically stabilized tetrahedral network toward an octahedral titania thin film with stress-relief from octahedral strontia units at the surface.
The newly sequenced mitochondrial genomes of 107 Asian swamp buffalo (Bubalus bubalis carabensis) allowed the reconstruction of the matrilineal divergence since ~900 Kya. Phylogenetic trees and ...Bayesian skyline plots suggest a role of the glacial periods in the demographic history of swamp buffalo. The ancestral swamp-buffalo mitogenome is dated ~232 ± 35 Kya. Two major macro-lineages diverged during the 2
Pleistocene Glacial Period (~200-130 Kya), but most (~99%) of the current matrilines derive from only two ancestors (SA1'2 and SB) that lived around the Last Glacial Maximum (~26-19 Kya). During the late Holocene optimum (11-6 Kya) lineages differentiated further, and at least eight matrilines (SA1, SA2, SB1a, SB1b, SB2a, SB2b, SB3 and SB4) were domesticated around 7-3 Kya. Haplotype distributions support an initial domestication process in Southeast Asia, while subsequent captures of wild females probably introduced some additional rare lineages (SA3, SC, SD and SE). Dispersal of domestic buffaloes created local population bottlenecks and founder events that further differentiated haplogroup distributions. A lack of maternal gene flow between neighboring populations apparently maintained the strong phylogeography of the swamp buffalo matrilines, which is the more remarkable because of an almost complete absence of phenotypic differentiation.
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