When deformed beyond their elastic limits, crystalline solids flow plastically via particle rearrangements localized around structural defects. Disordered solids also flow, but without obvious ...structural defects. We link structure to plasticity in disordered solids via a microscopic structural quantity, “softness,” designed by machine learning to be maximally predictive of rearrangements. Experimental results and computations enabled us to measure the spatial correlations and strain response of softness, as well as two measures of plasticity: the size of rearrangements and the yield strain. All four quantities maintained remarkable commonality in their values for disordered packings of objects ranging from atoms to grains, spanning seven orders of magnitude in diameter and 13 orders of magnitude in elastic modulus. These commonalities link the spatial correlations and strain response of softness to rearrangement size and yield strain, respectively.
Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently isolated bacterial species from polymicrobial infections of patients with cystic fibrosis and chronic wounds. We apply ...mass spectrometry guided interaction studies to determine how chemical interaction shapes the fitness and community structure during co-infection of these two pathogens. We demonstrate that S. aureus is equipped with an elegant mechanism to inactivate pyochelin via the yet uncharacterized methyltransferase Spm (staphylococcal pyochelin methyltransferase). Methylation of pyochelin abolishes the siderophore activity of pyochelin and significantly lowers pyochelin-mediated intracellular reactive oxygen species (ROS) production in S. aureus. In a murine wound co-infection model, an S. aureus mutant unable to methylate pyochelin shows significantly lower fitness compared with its parental strain. Thus, Spm-mediated pyochelin methylation is a mechanism to increase S. aureus survival during in vivo competition with P. aeruginosa.
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•Staphylococcus aureus methylates pyochelin produced by Pseudomonas aeruginosa•Pyochelin is methylated by the staphylococcal pyochelin methyltransferase (Spm)•Pyochelin loses its biological activity upon Spm-mediated methylation•Pyochelin methylation increases S. aureus fitness in co-infections with P. aeruginosa
Jenul et al. report that Staphylococcus aureus inactivates the Pseudomonas aeruginosa-derived siderophore pyochelin by methylation. Pyochelin methylation is dependent on the enzyme staphylococcal pyochelin methyltransferase (Spm) and increases S. aureus fitness in co-infections with P. aeruginosa.
Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to ...transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization.
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•There are two major divergent SasG alleles in S. aureus, SasG-I and SasG-II•SasG-II contains a nonaromatic arginine residue in the lectin-binding pocket•SasG-II has a different adhesion profile than SasG-I and binds a broader variety of ligands
Mills et al. show that Staphylococcus aureus surface protein G (SasG) has two major divergent alleles, SasG-I and SasG-II. SasG-II has a broader binding profile than SasG-I, which confers an advantage to these S. aureus SasG-II-expressing strains in colonizing human skin.
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to ...treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5
), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5
MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy.
First partial tropospheric ozone columns (0–6 km) derived from radiances observed by the IASI instrument aboard the MetOp‐A platform over Europe during summer 2007 are presented. They were retrieved ...using an altitude‐dependent regularization method. Comparison with measurements from balloon sondes shows excellent agreement. Space‐borne observations show large lower tropospheric ozone amounts over South‐Eastern Europe during the heat wave period, which are also displayed by simulations with a regional chemistry‐transport model CHIMERE.
A disordered material that cannot relax to equilibrium, such as an amorphous or glassy solid, responds to deformation in a way that depends on its past. In experiments we train a two-dimensional ...athermal amorphous solid with oscillatory shear, and show that a suitable readout protocol reveals the shearing amplitude. When shearing alternates between two amplitudes, signatures of both values are retained only if the smaller one is applied last. We show that these behaviors arise because individual clusters of rearrangements are hysteretic and dissipative, and because different clusters respond differently to shear. These roles for hysteresis and disorder are reminiscent of the return-point memory seen in ferromagnets and many other systems. Accordingly, we show how a simple model of a ferromagnet can reproduce key results of our experiments and of previous simulations. Unlike ferromagnets, amorphous solids' disorder is unquenched; they require “training” to develop this behavior.
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