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Nanomaterials acquire a biomolecular corona upon introduction to biological media, leading to biological transformations such as changes in protein function, unmasking of epitopes, and protein fibrilization. Ex vivo studies to investigate the effect of nanoparticles on protein–protein interactions are typically performed in buffer and are rarely measured quantitatively in live cells. Here, we measure the differential effect of silica nanoparticles on protein association in vitro vs. in mammalian cells. BtubA and BtubB are a pair of bacterial tubulin proteins identified inProsthecobacterstrains that self-assemble like eukaryotic tubulin, first into dimers and then into microtubules in vitro or in vivo. Förster resonance energy transfer labeling of each of the Btub monomers with a donor (mEGFP) and acceptor (mRuby3) fluorescent protein provides a quantitative tool to measure their binding interactions in the presence of unfunctionalized silica nanoparticles in buffer and in cells using fluorescence spectroscopy and microscopy. We show that silica nanoparticles enhance BtubAB dimerization in buffer due to protein corona formation. However, these nanoparticles have little effect on bacterial tubulin self-assembly in the complex mammalian cellular environment. Thus, the effect of nanomaterials on protein–protein interactions may not be readily translated from the test tube to the cell in the absence of particle surface functionalization that can enable targeted protein–nanoparticle interactions to withstand competitive binding in the nanoparticle corona from other biomolecules. 

Fusidic acid is a translation inhibitor with activity against major Gram-positive bacterial pathogens such as S. aureus. However, its activity against Gram-negatives is poor based on an inability to access its cytoplasmic target in these organisms. Opportunities for functionalization of the fusidic acid scaffold to enhance activity against Gram-negative pathogens have not been explored. Using an activity-guided synthetic strategy, the tolerance of the tetracyclic natural product to derivatization at the A- and C-rings and its carboxylic acid side chain was explored with the goal of enhancing its activity spectrum and pharmacological properties. All side-chain carboxylic acid esters were inactive. Oxidation of the C-ring alcohol and oxime were not tolerated either. A number of esters of the A-ring alcohol retained modest activity against Gram-positive bacteria and were informative for future activity-guided studies. For the A-ring esters, differences in antibacterial activity relative to inhibitory activity in a ribosome in vitro translation assay suggested the possibility of a pro-druglike effect for the fusidic acid pyrazine-2-carboxylate. This study furthers the understanding of the activity of the fusidic acid scaffold against Gram-positive bacteria. These results suggest promise for future modification of the A-ring alcohol of fusidic acid in the advancement of its antibiotic properties. 

We explore the Quantum Chromodynamics (QCD) phase diagram's complexities, including quark deconfinement transitions, liquid-gas phase changes, and critical points, using the chiral mean-field (CMF) model that is able to capture all these features. We introduce a vector meson renormalization within the CMF framework, enabling precise adjustments of meson masses and coupling strengths related to vector meson interactions. Performing a new fit to the deconfinement potential, we are able to replicate recent lattice QCD results, low energy nuclear physics properties, neutron star observational data, and key phase diagram features as per modern constraints. This approach enhances our understanding of vector mesons' roles in mediating nuclear interactions and their impact on the equation of state, contributing to a more comprehensive understanding of the QCD phase diagram and its implications for nuclear and astrophysical phenomena. 

Abstract Microbes are the drivers of soil phosphorus (P) cycling in terrestrial ecosystems; however, the role of soil microbes in mediating P cycling in P‐rich soils during primary succession remains uncertain. This study examined the impacts of bacterial community structure (diversity and composition) and its functional potential (absolute abundances of P‐cycling functional genes) on soil P cycling along a 130‐year glacial chronosequence on the eastern Tibetan Plateau. Bacterial community structure was a better predictor of soil P fractions than P‐cycling genes along the chronosequence. After glacier retreat, the solubilization of inorganic P and the mineralization of organic P were significantly enhanced by increased bacterial diversity, changed interspecific interactions, and abundant species involved in soil P mineralization, thereby increasing P availability. Although 84% of P‐cycling genes were associated with organic P mineralization, these genes were more closely associated with soil organic carbon than with organic P. Bacterial carbon demand probably determined soil P turnover, indicating the dominant role of organic matter decomposition processes in P‐rich alpine soils. Moreover, the significant decrease in the complexity of the bacterial co‐occurrence network and the taxa‐gene‐P network at the later stage indicates a declining dominance of the bacterial community in driving soil P cycling with succession. Our results reveal that bacteria with a complex community structure have a prominent potential for biogeochemical P cycling in P‐rich soils during the early stages of primary succession. 

Studies of proteins from one organism in another organism’s cells have shown that such exogenous proteins stick more, pointing toward coevolution of the cytoplasm and protein surface to minimize stickiness. Here we flip this question around by asking whether exogenous proteins can assemble efficiently into their target complexes in a non-native cytoplasm. We use as our model system the assembly of BtubA and BtubB from Prosthecobacter hosted in human U-2 OS cells. BtubA and B evolved from eukaryotic tubulins after horizontal gene transfer, but they have low surface sequence identity with the homologous human tubulins and do not respond to tubulin drugs such as nocodazole. In U-2 OS cells, BtubA and B assemble efficiently into dimers compared to in vitro, and the wild-type BtubA and B proteins subsequently are able to form microtubules as well. We find that generic crowding effects (Ficoll 70 in vitro) contribute significantly to efficient dimer assembly when compared to sticking interactions (U-2 OS cell lysate in vitro), consistent with the notion that a generic mechanism such as crowding can be effective at driving assembly of exogenous proteins, even when protein-cytoplasm quinary structure and sticking have been modified in a non-native cytoplasm. A simple Monte Carlo model of in vitro and in-cell interactions, treating BtubA and B as sticky dipoles in a matrix of sticky or nonsticky crowders, rationalizes all the experimental trends with two adjustable parameters and reveals nucleation as the likely mechanism for the time-scale separation between dimer- and tubule formation in-cell and in vitro. 

Abstract We present power spectra of the cosmic microwave background (CMB) anisotropy in temperature and polarization, measured from the Data Release 6 maps made from Atacama Cosmology Telescope (ACT) data. These cover 19,000 deg²of sky in bands centered at 98, 150 and 220 GHz, with white noise levels three times lower thanPlanckin polarization. We find that the ACT angular power spectra estimated over 10,000 deg², and measured to arcminute scales in TT, TE and EE, are well fit by the sum of CMB and foregrounds, where the CMB spectra are described by the ΛCDM model. Combining ACT with larger-scalePlanckdata, the joint P-ACT dataset provides tight limits on the ingredients, expansion rate, and initial conditions of the universe. We find similar constraining power, and consistent results, from either thePlanckpower spectra or from ACT combined withWMAPdata, as well as from either temperature or polarization in the joint P-ACT dataset. When combined with CMB lensing from ACT andPlanck, and baryon acoustic oscillation data from the Dark Energy Spectroscopic Instrument (DESI DR1), we measure a baryon density of Ω_bh²= 0.0226 ± 0.0001, a cold dark matter density of Ω_ch²= 0.118 ± 0.001, a Hubble constant ofH₀= 68.22 ± 0.36 km/s/Mpc, a spectral index ofn_s= 0.974 ± 0.003, and an amplitude of density fluctuations ofσ₈= 0.813 ± 0.005. Including the DESI DR2 data tightens the Hubble constant toH₀= 68.43 ± 0.27 km/s/Mpc; ΛCDM parameters agree between the P-ACT and DESI DR2 data at the 1.6σlevel. We find no evidence for excess lensing in the power spectrum, and no departure from spatial flatness. The contribution from Sunyaev-Zel'dovich (SZ) anisotropy is detected at high significance; we find evidence for a tilt with suppressed small-scale power compared to our baseline SZ template spectrum, consistent with hydrodynamical simulations with feedback. 

Abstract We present Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) maps of the Cosmic Microwave Background temperature and polarization anisotropy at arcminute resolution over three frequency bands centered on 98, 150 and 220 GHz. The maps are based on data collected with the AdvancedACT camera over the period 2017–2022 and cover 19,000 square degrees with a median combined depth of 10 μK arcmin. We describe the instrument, mapmaking and map properties and illustrate them with a number of figures and tables. The ACT DR6 maps and derived products are available on LAMBDA athttps://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html. We also provide an interactive web atlas athttps://phy-act1.princeton.edu/public/snaess/actpol/dr6/atlasand HiPS data sets in Aladin (e.g.https://alasky.cds.unistra.fr/ACT/DR4DR6/color_CMB).