71 research outputs found

    Turbulent drag on a low-frequency vibrating grid in superfluid He-4 at very low temperatures

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    We present measurements of the dissipative turbulent drag on a vibrating grid in superfluid He-4 over a wide range of (low) frequencies. At high velocities, the dissipative drag is independent of frequency and is approximately the same as that measured in normal liquid He-4. We present measurements on a similar grid in superfluid He-3-B at low temperatures which shows an almost identical turbulent drag coefficient at low frequencies. However, the turbulent drag in He-3-B is substantially higher at higher frequencies. We also present measurements of the inertial drag coefficient for grid turbulence in He-4. The inertial drag coefficient is significantly reduced by turbulence in both superfluid and normal liquid He-4

    Molecular bases determining daptomycin resistance-mediated re-sensitization to β-lactams ("see-saw effect") in MRSA

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    Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Methicillin-resistant Staphylococcus aureus (MRSA) are among the most difficult to treat in clinical settings due to the resistance to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic Daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy. Decreased susceptibility to DAP (DAPR) reported in MRSA is frequently accompanied with a paradoxical decrease in β-lactam resistance, a process known as the "see-saw" effect. Despite the observed discordance in resistance phenotypes, the combination of DAP/β-lactams has been proven clinically effective for the prevention and treatment of infections due to DAPR-MRSA strains. However, the mechanisms underlying the interactions between DAP and β-lactams are largely unknown. Herein, we studied the role of DAP-induced mutated mprF in β-lactam sensitization and its involvement in the effective killing by the DAP/OXA combination. DAP/OXA-mediated effects resulted in cell-wall perturbations including changes in peptidoglycan (PG) insertion, penicillin-binding protein 2 (PBP2) delocalization and reduced membrane amounts of penicillin-binding protein 2a (PBP2a) contents despite increased transcription of mecA through mec regulatory elements. We have found that the VraSR sensor-regulator is a key component of DAP resistance, triggering mutated mprF-mediated cell membrane (CM) modifications and resulting in impairment of PrsA location and chaperone functions, both essentials for PBP2a maturation, the key determinant of β-lactam resistance. These observations provide first time evidence that synergistic effects between DAP and β-lactams involve PrsA post-transcriptional regulation of CM-associated PBP2a

    Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

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    Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    Season and Genotype Influence Golf Ball Roll Distance on Creeping Bentgrass

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    Golfers are demanding increased ball roll distances on a daily basis, but cultural practices to achieve this often are detrimental to the green. One option for increasing ball roll distance without altering cultural practices may be to select creeping bentgrass genotypes that provide less resistance to ball roll. Studies were conducted at the John Seaton Anderson Turfgrass and Ornamental Research Facility near Ithaca, Neb., and at the Rocky Ford Turfgrass Research Facility in Manhattan, Kans., to determine genotype and seasonal influences on golf ball roll distance. Eighteen creeping bentgrass (Agrostis palustris Huds.) genotypes were evaluated. Genotype was not a significant source of variability, but the location Ă— season interaction was. Significant seasonal differences in ball roll occurred at both locations. Ball roll distances for spring, summer, and fall were 98,15, and 31 cm greater at the Nebraska test location than at the Kansas site. Correlations between turfgrass visual quality and ball roll distance were not significant. Therefore, the use of genotypes exhibiting high turfgrass visual quality will not necessarily result in longer ball rolls. Since there were no season Ă— genotype or genotype x location interactions, ball roll distance on genotypes at each location changed similarly with season. Genotype selection appears to have little influence on ball roll distance under the conditions tested at these two locations

    Functionalized blown films of plasticized polylactic acid/chitin nanocomposite: Preparation and characterization

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    cited By 8International audienceBionanocomposite films prepared with melt compounding and film blowing were evaluated for packaging applications. The nanocomposite masterbatch with 75 wt.% polylactic acid (PLA), 5 wt.% chitin nanocrystals (ChNCs) and 20 wt.% glycerol triacetate plasticizer (GTA) was melt compounded and then diluted to 1 wt.% ChNCs with PLA and polybutylene adipate-co-terephthalate (PBAT) prior to film blowing. The morphological, mechanical, optical, thermal and barrier properties of the blown nanocomposite films were studied and compared with the reference material without ChNCs. The addition of 1 wt.% ChNCs increased the tear strength by 175% and the puncture strength by 300%. Additionally, the small amount of chitin nanocrystals affected the glass transition temperature (Tg), which increased 4 °C compared with the reference material and slightly enhanced the films degree of crystallinity. The chitin nanocomposite also had lower fungal activity and lower electrostatic attraction between the film surfaces; leading to easy opening of the plastic bags. The barrier and optical properties as well as the thermal degradation of the films were not significantly influenced by the addition of chitin nanocrystals. © 2015 The Authors

    A New Device for Studying Low or Zero Frequency Mechanical Motion at Very Low Temperatures

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    We have developed a new "floppy wire" device for studying the motion through quantum fluids and solids at very low temperatures. The device is particularly well suited for producing large amplitudes of motion, for measuring drag forces at low frequency, and for studying "zero" frequency dynamics by measuring transient behavior. The device is very versatile and allows motion to be studied over a broad range of velocities and amplitudes. It generates negligible heat leaks and so is ideally suited for ultra low temperature experiments. The device has many potential applications in quantum fluids and solids research, including the study of drag forces at low frequencies in both the laminar and turbulent flow regimes, and the investigation of motion in (super)solid (4)He. We discuss the principles and modes of operation of the device and present some preliminary measurements in vacuum, in normal liquid (3)He and in superfluid (4)He. We also present measurements of a "floppy grid" device, which could be used for generating large volumes of quantum turbulence in superfluids at low temperatures
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