77 research outputs found

    <em>In silico</em> analysis of bacterial arsenic islands reveals remarkable synteny and functional relatedness between arsenate and phosphate

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    In order to construct a more universal model for understanding the genetic requirements for bacterial AsIII oxidation, an in silico examination of the available sequences in the GenBank was assessed and revealed 21 conserved 5–71 kb arsenic islands within phylogenetically diverse bacterial genomes. The arsenic islands included the AsIII oxidase structural genes aioBA, ars operons (e.g., arsRCB) which code for arsenic resistance, and pho, pst, and phn genes known to be part of the classical phosphate stress response and that encode functions associated with regulating and acquiring organic and inorganic phosphorus. The regulatory genes aioXSR were also an island component, but only in Proteobacteria and orientated differently depending on whether they were in α-Proteobacteria or β-/γ-Proteobacteria. Curiously though, while these regulatory genes have been shown to be essential to AsIII oxidation in the Proteobacteria, they are absent in most other organisms examined, inferring different regulatory mechanism(s) yet to be discovered. Phylogenetic analysis of the aio, ars, pst, and phn genes revealed evidence of both vertical inheritance and horizontal gene transfer (HGT). It is therefore likely the arsenic islands did not evolve as a whole unit but formed independently by acquisition of functionally related genes and operons in respective strains. Considering gene synteny and structural analogies between arsenate and phosphate, we presumed that these genes function together in helping these microbes to be able to use even low concentrations of phosphorus needed for vital functions under high concentrations of arsenic, and defined these sequences as the arsenic islands

    The influence of adatom diffusion on the formation of skyrmion lattice in sub-monolayer Fe on Ir(111)

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    Room temperature grown Fe monolayer (ML) on the Ir(111) single crystal substrate has attracted great research interests as nano-skyrmion lattice can form under proper growth conditions. The formation of the nanoscale skyrmion, however, appears to be greatly affected by the diffusion length of the Fe adatoms on the Ir(111) surface. We made this observation by employing spin-polarized scanning tunneling microscopy to study skyrmion formation upon systematically changing the impurity density on the substrate surface prior to Fe deposition. Since the substrate surface impurities serve as pinning centers for Fe adatoms, the eventual size and shape of the Fe islands exhibit a direct correlation with the impurity density, which in turn determines whether skyrmion can be formed. Our observation indicates that skyrmion only forms when the impurity density is below 0.006/nm2, i.e., 12 nm averaged spacing between the neighboring defects. We verify the significance of Fe diffusion length by growing Fe on clean Ir(111) substrate at low temperature of 30 K, where no skyrmion was observed to form. Our findings signify the importance of diffusion of Fe atoms on the Ir(111) substrate, which affects the size, shape and lattice perfection of the Fe islands and thus the formation of skyrmion lattice

    Creation of nano-skyrmion lattice in Fe/Ir(111) system using voltage pulse

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    Magnetic ultrathin films grown on heavy metal substrates often exhibit rich spin structures due to the competition between various magnetic interactions such as Heisenberg exchange, Dzyaloshinskii-Moriya interaction and higher-order spin interactions. Here we employ spin-polarized scanning tunneling microscopy to study magnetic nano-skyrmion phase in Fe monolayer grown on Ir(111) substrate. Our observations show that the formation of nano-skyrmion lattice in the Fe/Ir(111) system depends sensitively on the growth conditions and various non-skyrmion spin states can be formed. Remarkably, the application of voltage pulses between the tip and the sample can trigger a non-skyrmion to skyrmion phase transition. The fact that nano-skyrmions can be created using voltage pulse indicates that the balance between the competing magnetic interactions can be affected by an external electric field, which is highly useful to design skyrmion-based spintronic devices with low energy consumption

    Case report: Compound heterozygous mutations in the KDSR gene cause progressive keratodermia and thrombocytopenia

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    KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in KDSR that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient

    Origin of defect-related green emission from ZnO nanoparticles: effect of surface modification

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    We investigated the optical properties of colloidal-synthesized ZnO spherical nanoparticles prepared from 1-octadecene (OD), a mixture of trioctylamine (TOA) and OD (1:10), and a mixture of trioctylphosphine oxide (TOPO) and OD (1:12). It is found that the green photoluminescence (PL) of samples from the mixture of TOA/OD and TOPO/OD is largely suppressed compared with that from pure OD. Moreover, it is found that all spherical nanoparticles have positive zeta potential, and spherical nanoparticles from TOA/OD and TOPO/OD have a smaller zeta potential than those from OD. A plausible explanation is that oxygen vacancies, presumably located near the surface, contribute to the green PL, and the introduction of TOA and TOPO will reduce the density of oxygen vacancies near the surfaces. Assuming that the green emission arises due to radiative recombination between deep levels formed by oxygen vacancies and free holes, we estimate the size of optically active spherical nanoparticles from the spectral energy of the green luminescence. The results are in good agreement with results from TEM. Since this method is independent of the degree of confinement, it has a great advantage in providing a simple and practical way to estimate the size of spherical nanoparticles of any size. We would like to point out that this method is only applicable for samples with a small size distribution

    Membrane Vesicles Are the Dominant Structural Components of Ceftazidime-Induced Biofilm Formation in an Oxacillin-Sensitive MRSA

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    Methicillin-resistant Staphylococcus aureus (MRSA) has received increasing attention in recent years. However, the characteristics and relevant mechanisms of biofilm formation in oxacillin-sensitive MRSA (OS-MRSA) are poorly understood. This study was designed to characterize biofilm formation in OS-MRSA BWSA15 in response to ceftazidime (TZ) by comparing the methicillin-sensitive S. aureus (MSSA) strain BWSA23 and the oxacillin-resistant MRSA (OR-MRSA) strain BWSA11. The biofilms and biofilm-forming cells were observed by electron microscopy. Biofilms grown on microtiter plates were chemically decomposed and analyzed by Fourier transform infrared spectroscopy. The transcriptional regulation of genes associated with methicillin resistance, surface adhesion, fatty acid biosynthesis, and global regulation (sigma B) was investigated. A significant increase in biofilm formation ability (10.21-fold) and aggregation ability (2.56-fold) was observed in BWSA15 upon the treatment with TZ (16 ÎĽg/ml). The TZ-induced biofilm formation in BWSA15 was characterized by a disappearance of polysaccharide-like extracellular substances and an appearance of a large number of intercellular MVs from extracellular matrix. Few MVs were identified in the biofilms formed by BWSA11 and BWSA23. There was a significant upregulation of mecA, sigB, and fatty acid biosynthesis-associated genes and downregulation of icaA, icaD, clfA, clfB, and fnaA in BWSA15 upon the treatment with TZ. The formation of intracellular junctions of MVs in the biofilms of BWSA15 was mediated by a significant increase in the proportion of proteins as well as by an increase in the proportion of non-ionized carboxyl groups in fatty acids. This study demonstrated that beta-lactam antibiotics can induce biofilm formation in OS-MRSA, and the biofilm induction in OS-MRSA can mainly be attributed to exposed MVs with increased hydrophobicity rather than polysaccharide intercellular adhesins, cell wall-anchored surface proteins, and extracellular DNA

    Automatic assessment of glioma burden: A deep learning algorithm for fully automated volumetric and bi-dimensional measurement

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    Background Longitudinal measurement of glioma burden with MRI is the basis for treatment response assessment. In this study, we developed a deep learning algorithm that automatically segments abnormal fluid attenuated inversion recovery (FLAIR) hyperintensity and contrast-enhancing tumor, quantitating tumor volumes as well as the product of maximum bidimensional diameters according to the Response Assessment in Neuro-Oncology (RANO) criteria (AutoRANO). Methods Two cohorts of patients were used for this study. One consisted of 843 preoperative MRIs from 843 patients with low- or high-grade gliomas from 4 institutions and the second consisted of 713 longitudinal postoperative MRI visits from 54 patients with newly diagnosed glioblastomas (each with 2 pretreatment “baseline” MRIs) from 1 institution. Results The automatically generated FLAIR hyperintensity volume, contrast-enhancing tumor volume, and AutoRANO were highly repeatable for the double-baseline visits, with an intraclass correlation coefficient (ICC) of 0.986, 0.991, and 0.977, respectively, on the cohort of postoperative GBM patients. Furthermore, there was high agreement between manually and automatically measured tumor volumes, with ICC values of 0.915, 0.924, and 0.965 for preoperative FLAIR hyperintensity, postoperative FLAIR hyperintensity, and postoperative contrast-enhancing tumor volumes, respectively. Lastly, the ICCs for comparing manually and automatically derived longitudinal changes in tumor burden were 0.917, 0.966, and 0.850 for FLAIR hyperintensity volume, contrast-enhancing tumor volume, and RANO measures, respectively. Conclusions Our automated algorithm demonstrates potential utility for evaluating tumor burden in complex posttreatment settings, although further validation in multicenter clinical trials will be needed prior to widespread implementation

    Precision mouse models with expanded tropism for human pathogens

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    A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics
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