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9%), both in MSSA and MRSA isolates. Presence of genes encoding for the enterotoxins (sea, seb, sec, seh, sek), exfoliative toxin A (eta), and toxic shock syndrome toxin-1 (tst) was also observed. Strains carrying lukS-PV/lukF-PV genes belonged to SCCmecV- spa type t437. The most prevalent spa types were t091, t015, t084, t002, t571, and t026 among all 57 identified. Spa types, including 3 new ones, grouped in 6 different spa-CC clonal complexes, with four major dominated; CC45, CC30, CC5, and CC15. This study demonstrated that both methicillin-susceptible and methicillin-resistant major European clones of S. aureus could be isolated from the oral cavity of dental patients, with the emergence of PVL-positive CA-MRSA strains. The oral cavity should be considered as a possible source of toxigenic egc-positive S. aureus strains, in terms of potential risk of cross-infection and dissemination to other body sites.Streptococcus pneumoniae (pneumococcus) is a principal cause of bacterial middle ear infections, pneumonia, and meningitis. Capsule-targeted pneumococcal vaccines have likely contributed to increased carriage of nonencapsulated S. pneumoniae (NESp). Some NESp lineages are associated with highly efficient DNA uptake and transformation frequencies. However, NESp strains lack capsule that may increase disease severity. We tested the hypothesis that NESp could acquire capsule during systemic infection and transform into more virulent pneumococci. We reveal that NESp strains MNZ67 and MNZ41 are highly transformable and resistant to multiple antibiotics. Natural transformation of NESp when co-administered with heat-killed encapsulated strain WU2 in a murine model of systemic infection resulted in encapsulation of NESp and increased virulence during bacteremia. Functional capsule production increased the pathogenic potential of MNZ67 by significantly decreasing complement deposition on the bacterial surface. However, capsule acquisition did not further decrease complement deposition on the relatively highly pathogenic strain MNZ41. Whole genome sequencing of select transformants demonstrated that recombination of up to 56.7 kbp length occurred at the capsule locus, along with additional recombination occurring at distal sites harboring virulence-associated genes. These findings indicate NESp can compensate for lack of capsule production and rapidly evolve into more virulent strains.In this work, nickel cobaltite (NiCo2O4) nanosheets with a porous structure were fabricated on nickel foam as a working electrode for supercapacitor applications. The nanosheets were fabricated by electrochemical deposition of nickel-cobalt hydroxide on the nickel foam substrate at ambient temperature in a three-electrode cell followed by annealing at 300 °C to transform the coating into a porous NiCo2O4 nanosheet. Field emission scanning electron microscopy and transmission electron microscopy revealed a three-dimensional mesoporous structure, which facilitates ion transport and electronic conduction for fast redox reactions. For one cycle, the NiCo2O4 electrodeposited nickel foam has a high specific capacitance (1734.9 F g-1) at a current density (CD) of 2 A g-1. The electrode capacitance decreased by only approximately 12.7% after 3500 cycles at a CD of 30 A g-1. Moreover, a solid-state asymmetric supercapacitor (ASC) was built utilising the NiCo2O4 nanosheets, carbon nanotubes, and a polyvinyl alcohol-potassium hydroxide gel as the anode, cathode, and solid-state electrolyte, respectively. The ASC displayed great electrochemical properties with a 42.25 W h kg-1 energy density at a power density of 298.79 W kg-1.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Inhibition of the kinase ATR, a central regulator of the DNA damage response, eliminates subsets of cancer cells in certain tumors. As previously shown, this is at least partly attributable to synthetic lethal interactions between ATR and POLD1, the catalytic subunit of the polymerase δ. Various POLD1 variants have been found in colorectal cancer, but their significance as therapeutic targets for ATR pathway inhibition remains unknown. Using CRISPR/Cas9 in the colorectal cancer cell line DLD-1, which harbors four POLD1 variants, we established heterozygous POLD1-knockout clones with exclusive expression of distinct variants to determine the functional relevance of these variants individually by assessing their impact on ATR pathway activation, DNA replication, and cellular sensitivity to inhibition of ATR or its effector kinase CHK1. Of the four variants analyzed, only POLD1R689W affected POLD1 function, as demonstrated by compensatory ATR pathway activation and impaired DNA replication. Upon treatment with ATR or CHK1 inhibitors, POLD1R689W strongly decreased cell survival in vitro, which was attributable at least partly to S phase impairment and apoptosis. Similarly, treatment with the ATR inhibitor AZD6738 inhibited growth of murine xenograft tumors, harboring the POLD1R689W variant, in vivo. Our POLD1-knockout model thus complements algorithm-based models to predict the pathogenicity of tumor-specific variants of unknown significance and illustrates a novel and potentially clinically relevant therapeutic approach using ATR/CHK1 inhibitors in POLD1-deficient tumors.Shifting climate patterns may impose novel combinations of abiotic conditions on animals, yet understanding of the present-day interactive effects of multiple stressors remains under-developed. We tested the oxygen and capacity limited thermal tolerance (OCLTT) hypothesis and quantified environmental preference of the copepod Tigriopus californicus, which inhabits rocky-shore splashpools where diel fluctuations of temperature and dissolved oxygen (DO) are substantial. Selleckchem SL-327 Egg-mass bearing females were exposed to a 5 h heat ramp to peak temperatures of 34.1-38.0 °C crossed with each of four oxygen levels 22, 30, 100 and 250% saturation (4.7-5.3, 5.3-6.4, 21.2-21.3, and 50.7-53.3 kPa). Survival decreased at higher temperatures but was independent of DO. The behavioral preference of females was quantified in seven combinations of gradients of both temperature (11-37 °C) and oxygen saturation (17-206% or 3.6-43.6 kPa). Females avoided high temperatures regardless of DO levels. This pattern was more pronounced when low DO coincided with high temperature.
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