Previous studies showed that sub-MIC levels of β-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process ...by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions. We also found that USA300 biofilms cultured in sub-MIC amoxicillin were thicker, contained more pillar and channel structures, and were less porous than biofilms cultured without antibiotic. Biofilm formation in sub-MIC amoxicillin correlated with the production of extracellular DNA (eDNA). However, eDNA released by amoxicillin-induced cell lysis alone was evidently not sufficient to stimulate biofilm. Sub-MIC levels of two other cell wall-active agents with different mechanisms of action-d-cycloserine and fosfomycin-also stimulated eDNA-dependent biofilm, suggesting that biofilm formation may be a mechanistic adaptation to cell wall stress. Screening a USA300 mariner transposon library for mutants deficient in biofilm formation in sub-MIC amoxicillin identified numerous known mediators of S. aureus β-lactam resistance and biofilm formation, as well as novel genes not previously associated with these phenotypes. Our results link cell wall stress and biofilm formation in MRSA and suggest that eDNA-dependent biofilm formation by strain USA300 in low-dose amoxicillin is an inducible phenotype that can be used to identify novel genes impacting MRSA β-lactam resistance and biofilm formation.
Heterogeneity of Popular Boys Rodkin, Philip C; Farmer, Thomas W; Pearl, Ruth ...
Developmental psychology,
01/2000, Letnik:
36, Številka:
1
Journal Article
Recenzirano
Odprti dostop
This study examined subtypes of popular 4th-6th grade boys (
N
= 452). Popular-prosocial (model) and popular-antisocial (tough) configurations were identified by means of teacher ratings and compared ...with peer and self-assessments and social centrality measures. Peers perceived model boys as cool, athletic, leaders, cooperative, studious, not shy, and nonaggressive. Peers perceived tough boys as cool, athletic, and antisocial. Model boys saw themselves as nonaggressive and academically competent. Tough boys saw themselves as popular, aggressive, and physically competent. Tough boys were disproportionately African American, particularly when African Americans were a minority in their classrooms. Model and tough boys were overrepresented at nuclear social centrality levels. These findings suggest that highly aggressive boys can be among the most popular and socially connected children in elementary classrooms.
Organ development involves the sustained production of diverse cell types with spatiotemporal precision. In the vertebrate jaw, neural-crest-derived progenitors produce not only skeletal tissues but ...also later-forming tendons and salivary glands. Here we identify the pluripotency factor Nr5a2 as essential for cell-fate decisions in the jaw. In zebrafish and mice, we observe transient expression of Nr5a2 in a subset of mandibular postmigratory neural-crest-derived cells. In zebrafish nr5a2 mutants, nr5a2-expressing cells that would normally form tendons generate excess jaw cartilage. In mice, neural-crest-specific Nr5a2 loss results in analogous skeletal and tendon defects in the jaw and middle ear, as well as salivary gland loss. Single-cell profiling shows that Nr5a2, distinct from its roles in pluripotency, promotes jaw-specific chromatin accessibility and gene expression that is essential for tendon and gland fates. Thus, repurposing of Nr5a2 promotes connective tissue fates to generate the full repertoire of derivatives required for jaw and middle ear function.
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•Pluripotency gene Nr5a2 redeployed in neural-crest-derived mesenchyme•Nr5a2 restricts cartilage specification in fish jaw and mouse middle ear•Essential role for Nr5a2 in jaw tendon and salivary gland formation•Nr5a2 ensures jaw enhancer accessibility for nonskeletal multilineage potential
In this study, Chen et al. identify a conserved function of the nuclear receptor Nr5a2 in patterning the zebrafish and mouse lower jaw and mouse middle ear. They find that Nr5a2 opens up regions of the genome that are essential for tendon and salivary gland development at the expense of skeleton formation.
MicroRNAs in ectodermal appendages Farmer, D’Juan T; McManus, Michael T
Current opinion in genetics & development,
04/2017, Letnik:
43
Journal Article
Recenzirano
The surface ectoderm is the source of ectodermal appendages including hair, teeth, and many glands. The development and function of ectodermal appendages has been researched extensively, but many of ...the molecular mechanisms that govern the developmental programs of ectodermal appendages remain elusive. While several protein-coding genes are established as key regulators of ectodermal appendage development, the role of noncoding RNAs is an emerging area of investigation. This review highlights recent advances in studies of microRNA-mediated control of ectodermal appendage development using mouse models. We will also discuss future directions and technological advances that will drive the microRNA field forward and expand our understanding of how individual microRNAs control ectodermal appendage development.
MicroRNAs are small noncoding RNAs thought to have pivotal roles in numerous diseases and developmental processes. However, a growing body of literature indicates that in vivo elimination of these ...tiny RNAs usually has little to no observable consequence, suggesting functional redundancy with other microRNAs or cellular pathways. We provide an in-depth analysis of miR-205 expression and define miR-205 as an epithelial-specific microRNA, and for the first time show that ablation of this microRNA knockout exhibits partially penetrant lethality in a constitutive mouse knockout model. Given the role of this microRNA in cancer and development, this mouse model will be an incredible reagent to study the function and mechanisms of miR-205 in epithelial tissue development and disease.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been used to generate ion images of samples in one or more mass-to-charge (m/z) values, providing the capability of ...mapping specific molecules to two-dimensional coordinates of the original sample. The high sensitivity of the technique (low-femtomole to attomole levels for proteins and peptides) allows the study of organized biochemical processes occurring in, for example, mammalian tissue sections. The mass spectrometer is used to determine the molecular weights of the molecular in the surface layers of the tissue. Molecules desorbed from the sample typically are singly protonated, giving an ion at (M + H)+, where M is the molecular mass. The procedure involves coating the tissue section, or a blotted imprint of the section, with a thin layer of energy-absorbing matrix and then analyzing the sample to produce an ordered array of mass spectra, each containing nominal m/z values typically covering a range of over 50,000 Da. Images can be displayed in individual m/z values as a selected ion image, which would localize individual compounds in the tissue, or as summed ion images. MALDI ion images of tissue sections can be obtained directly from tissue slices following preparative steps, and this is demonstrated for the mapping of insulin contained in an islet in a section of rat pancreas, hormone peptides in a small area of a section of rat pituitary, and a small protein bound to the membrane of human mucosa cells. Alternatively, imprints of the tissue can be analyzed by blotting the tissue sections on specially prepared targets containing an adsorbent material, e.g., C-18 coated resin beads. Peptides and small proteins bind to the C-18 and create a positive imprint of the tissue which can then be imaged by the mass spectrometer. This is demonstrated for the MALDI ion image analysis of regions of rat splenic pancreas and for an area of rat pituitary traversing the anterior, intermediate, and posterior regions where localized peptides were mapped. In a single spectrum from the anterior/intermediate lobe of a rat pituitary print, over 50 ions corresponding to the peptides present in this tissue were observed as well as precursors, isoforms, and metabolic fragments.
Simple scoping models that can be used to evaluate ATF performance under severe accident conditions have been developed. The methodology provides a fundamental technical basis (a.k.a. metric) based ...on the thermodynamic boundary for evaluating performance relative to that of traditional Zr-based claddings. The initial focus in this study was on UO2 fuel with the advanced claddings 310SS, D9, FeCrAl, and SiC. The evaluation considered only energy release with concurrent combustible gas production from fuel–cladding–coolant interactions and, separately, molten core–concrete interactions at high temperatures. Other important phenomenological effects that can influence the rate and extent of cladding decomposition (e.g., eutectic interactions, degradation of other core constituents) were not addressed. For the cladding types addressed, potential combustible gas production under both in-vessel and ex-vessel conditions was similar to that for Zr. However, exothermic energy release from cladding oxidation was substantially less for iron-based alloys (by at least a factor of 4), and modestly less (by ∼20%) for SiC. Data on SiC-clad UO2 fuel performance under severe accident conditions are sparse in the literature; thus, assumptions on the nature of the cladding decomposition process were made in order to perform this initial screening evaluation. Experimental data for this system under severe accident conditions is needed for a proper evaluation and comparison to iron-based claddings.
•Critical analysis of municipal waste management practices and performance in England.•Trends visualised via innovative ternary plots and changes and reasons explored.•Performance 1996–2013 moved ...slowly away from landfill dominance.•Large variations in %s of waste landfilled, incinerated and recycled/composted.•Progress to resource efficiency slow; affected by poor planning and hostile disputes.
European nations are compelled to reduce reliance on landfill as a destination for household waste, and should, in principle, achieve this goal with due recognition of the aims and principles of the waste hierarchy. Past research has predominantly focused on recycling, whilst interactions between changing waste destinies, causes and drivers of household waste management change, and potential consequences for the goal of the waste hierarchy are less well understood. This study analysed Local Authority Collected Waste (LACW) for England, at national, regional and sub-regional level, in terms of the destination of household waste to landfill, incineration and recycling. Information about waste partnerships, waste management infrastructure and collection systems was collected to help identify and explain changes in waste destinies. Since 1996, the proportion of waste landfilled in England has decreased, in tandem with increases in recycling and incineration. At the regional and sub-regional (Local Authority; LA) level, there have been large variations in the relative proportions of waste landfilled, incinerated and recycled or composted. Annual increases in the proportion of household waste incinerated were typically larger than increases in the proportion recycled. The observed changes took place in the context of legal and financial drivers, and the circumstances of individual LAs (e.g. landfill capacity) also explained the changes seen. Where observed, shifts from landfill towards incineration constitute an approach whereby waste management moves up the waste hierarchy as opposed to an attempt to reach the most preferred option(s); in terms of resource efficiency, this practice is sub-optimal. The requirement to supply incinerators with a feedstock over their lifespan reduces the benefits of developing of recycling and waste reduction, although access to incineration infrastructure permits short-term and marked decreases in the proportion of LACW landfilled. We conclude that there is a need for clearer national strategy and co-ordination to inform and guide policy, practice, planning and investment in infrastructure such that waste management can be better aligned with the principles of the circular economy and resource efficiency. If the ongoing stand-off between national political figures and the waste sector continues, England’s waste policy remains destined for indecision.
To understand controlling factors for seismogenesis and strain‐accumulation in subduction megathrusts we examine seismicity patterns across Nicoya, Costa Rica, to determine the overall and spatial ...variability in the earthquake frequency‐magnitude distribution along the interface. The mean reduction in earthquake activity with magnitude, b‐value, is higher (1.06) than global subduction zone averages (0.6–0.8), suggesting the interface here is weakly coupled. Strong spatial variations in b are anticorrelated (−0.53) with geodetic estimates of interface locking of E. Norabuena et al. (2004). High b prevails in two regions, including the subducted Fisher seamount chain. A broad zone of reduced b is observed at and offshore the central Nicoya coast; extending towards an imaged locked patch. These results suggest b‐value studies may be useful in identifying regions of increased interface locking in subduction zones, which may indicate regions capable of large slip in future large earthquakes.
Paenibacillus polymyxa is a Gram-positive bacterium commonly found associated with plant roots. P. polymyxa can exhibit two forms of flagellar motility: swimming in liquid culture and swarming on a ...surface. Here, swimming cells were compared to swarming cells using an integrated proteomic and lipidomic approach, yielding information about how lipid modifications and protein/enzyme pathways are tailored for these specific phenotypes. Observed differences in both phospholipid composition and metabolism between the two conditions suggest membrane remodeling in response to the surrounding environment. Key enzymes involved in glycerophospholipid metabolism were abundant in swimming bacteria, while enzymes associated with glycerol-3-phosphate metabolism were more abundant in swarming bacteria. Several glycoside hydrolases were either unique to or more abundant during swarming. This likely reflects the degradation of their own exopolysaccharides to both enhance swarming and supply the necessary chemical energy to compensate for increased flagellar synthesis. The observed upregulation of biosynthetic gene clusters (polyketides, lantibiotics, and surfactin) in swarming bacteria suggest the importance of signaling, antimicrobial activity, and surfactin production during this mode of motility – the latter of which is confirmed via RT-PCR.
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