A New Microarray System to Detect Streptococcus pneumoniae Serotypes

Streptococcus pneumoniae, one of the most common gram-positive pathogens to colonize the human upper respiratory tract, is responsible for many severe infections, including meningitis and bacteremia. A 23-valent pneumococcal vaccine is available to protect against the 23 S. pneumoniae serotypes responsible for 90% of reported bacteremic infections. Unfortunately, current S. pneumoniae serotype testing requires a large panel of expensive antisera, assay results may be subjective, and serotype cross-reactions are common. For this study, we designed an oligonucleotide-based DNA microarray to identify glycosyltransferase gene sequences specific to each vaccine-related serotype. Out of 56 isolates representing different serotypes, only one isolate, representing serotype 23A, was not detected correctly as it could not be distinguished from serotype 23F. Our data suggest that the microarray provides a more cost-effective and reliable way of monitoring pneumococcal capsular types

Variations in amount of TSST-1 produced by clinical methicillin resistant Staphylococcus aureus (MRSA) isolates and allelic variation in accessory gene regulator (agr) locus

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>(S. aureus) is an important pathogen associated with both nosocomial and community-acquired infections and its pathogenicity is attributed to its potential to produce virulence factors. Since the amount of toxin produced is related to virulence, evaluating toxin production should be useful for controlling S. aureus infection. We previously found that some strains produce relatively large amounts of TSST-1; however, no reports have described the amount of TSST-1 produced by clinical isolates.</p> <p>Methods</p> <p>Amounts of TSST-1 produced by clinical methicillin resistant S. aureus (MRSA) isolates were measured by Western blotting. We determined their accessory gene regulator (<it>agr</it>) class by PCR and investigated whether TSST-1 production correlates with variations in the class and structure of the <it>agr</it>.</p> <p>Results</p> <p>We found that 75% of surveyed MRSA isolates (n = 152) possessed the <it>tst </it>gene and that 96.7% belonged to <it>agr </it>class 2. The concentrations of TSST-1 secreted into culture supernatants by 34 strains measured by Western blotting differed 170-fold. Sequencing the entire <it>agr </it>locus (n = 9) revealed that some had allelic variations regardless of the amount of TSST-1 produced whereas sequencing the <it>sar</it>, sigma factor B and the <it>tst </it>promoter region revealed no significant changes.</p> <p>Conclusion</p> <p>The amounts of TSST-1 produced by clinical MRSA isolates varied. The present results suggest that TSST-1 production is not directly associated with the <it>agr </it>structure, but is instead controlled by unknown transcriptional/translational regulatory systems, or synthesized by multiple regulatory mechanisms that are interlinked in a complex manner.</p

High resolution imaging of molecular line emission from high redshift QSOs

We present moderate (1'') and high resolution (0.2'') observations of the CO(2-1) emission at 43 GHz, and radio continuum emission at 1.47 GHz, from the z=4.7 QSO BRI 1202-0725 and the z=4.4 QSO BRI 1335--0417 using the Very Large Array. The moderate resolution observations show that in both cases the CO emission is spatially resolved into two components separated by 1'' for 1335-0417 and 4'' for 1202-0725. The high resolution observations show that each component has sub-structure on scales of 0.2'' to 0.5'', with intrinsic brightness temperatures > 20K. The CO ladder from (2-1) up to (7-6) suggests a high kinetic temperature for the gas (70 K), and a high column density (10^{24} cm^{-2}). In both sources the continuum-to-line ratio: L_{FIR}/L'_{CO(1-0)} = 335. All these characteristics (brightness temperature, excitation temperature, column density, and continuum-to-line ratio) are comparable to conditions found in low redshift, ultra-luminous nuclear starburst galaxies. We find that the CO emitting regions in 1202-0725 and 1335-0417 must be close to face-on in order to avoid having the gas mass exceed the gravitational mass, implying perhaps unreasonably large rotational velocities. While this problem is mitigated by lowering the CO luminosity-to-H_2 mass conversion factor (X), the required X values become comparable to, or lower than, the minimum values dictated by optically thin CO emission. We considered the possibility of magnification by gravitational lensing in order to reduce the molecular gas masses.Comment: aastex 12 postscript figures. to appear in the Astronomical Journa

Transmission of bacterial infections to healthcare workers during intubation and respiratory care of patients with severe pneumonia

Exposure of healthcare workers to patients with rapidly fatal infections invariably raises concerns regarding the risk of occupational acquisition. We describe acquisition of Streptococcus pyogenes by 2 nurses from a patient with fatal pneumonia and review previously reported cases of transmission of bacterial pathogens from patients with pneumonia to healthcare workers

A regioselective and common synthetic method of dihalogenoindoles and its application for the total syntheses of marine alkaloids, 4,6-dibromo-,4,6-dibromo-2-methyl-, and 3,4,5-tribromoindole

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report

Background: Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants. Case presentation: A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months. Conclusions: Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM

Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart

ヒトiPS細胞由来心筋細胞の生着能改善に向けた新しい方法. 京都大学プレスリリース. 2023-07-14.Am80, a retinoic acid receptor agonist, activates cell cycle in induced cardiomyocytes and enhances heart tissue engraftment. 京都大学プレスリリース. 2023-07-14.Human induced pluripotent stem cell-derived (hiPSC) cardiomyocytes are a promising source for regenerative therapy. To realize this therapy, however, their engraftment potential after their injection into the host heart should be improved. Here, we established an efficient method to analyze the cell cycle activity of hiPSC cardiomyocytes using a fluorescence ubiquitination-based cell cycle indicator (FUCCI) system. In vitro high-throughput screening using FUCCI identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC cardiomyocytes. The transplantation of hiPSC cardiomyocytes treated with Am80 before the injection significantly enhanced the engraftment in damaged mouse heart for 6 months. Finally, we revealed that the activation of endogenous Wnt pathways through both RARA and RARB underlies the Am80-mediated cell cycle activation. Collectively, this study highlights an efficient method to activate cell cycle in hiPSC cardiomyocytes by Am80 as a means to increase the graft size after cell transplantation into a damaged heart

Comparative proteomic analysis of Salmonella enterica serovar Typhimurium ppGpp-deficient mutant to identify a novel virulence protein required for intracellular survival in macrophages

<p>Abstract</p> <p>Background</p> <p>The global ppGpp-mediated stringent response in pathogenic bacteria plays an important role in the pathogenesis of bacterial infections. In <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium), several genes, including virulence genes, are regulated by ppGpp when bacteria are under the stringent response. To understand the control of virulence genes by ppGpp in <it>S</it>. Typhimurium, agarose 2-dimensional electrophoresis (2-DE) combined with mass spectrometry was used and a comprehensive 2-DE reference map of amino acid-starved <it>S</it>. Typhimurium strain SH100, a derivative of ATCC 14028, was established.</p> <p>Results</p> <p>Of the 366 examined spots, 269 proteins were successfully identified. The comparative analysis of the wild-type and ppGpp⁰mutant strains revealed 55 proteins, the expression patterns of which were affected by ppGpp. Using a mouse infection model, we further identified a novel virulence-associated factor, STM3169, from the ppGpp-regulated and <it>Salmonella</it>-specific proteins. In addition, <it>Salmonella </it>strains carrying mutations in the gene encoding STM3169 showed growth defects and impaired growth within macrophage-like RAW264.7 cells. Furthermore, we found that expression of <it>stm3169 </it>was controlled by ppGpp and SsrB, a response regulator of the two-component system located on <it>Salmonella </it>pathogenicity island 2.</p> <p>Conclusions</p> <p>A proteomic approach using a 2-DE reference map can prove a powerful tool for analyzing virulence factors and the regulatory network involved in <it>Salmonella </it>pathogenesis. Our results also provide evidence of a global response mediated by ppGpp in <it>S. enterica</it>.</p

Enhancement of coercive field in atomically-thin quenched Fe5GeTe2

We have fabricated thin films of a van der Waals (vdW) ferromagnetic metal Fe₅GeTe₂ and characterized them by measuring the anomalous Hall effect. While the bulk Fe₅GeTe₂ does not exhibit a perpendicular magnetic anisotropy (PMA) unlike Fe₃GeTe₂, PMA emerges in the thin film devices. Furthermore, the PMA is enhanced with decreasing thickness of Fe₅GeTe₂. In particular, a thin film (5 unit-cell layer) device fabricated with Fe₅GeTe₂ quenched at 1050 K has two times larger coercive field than that prepared without quenching. Such a PMA should be useful for future vdW spintronic devices