Role of OmpD2 and chromosomal P-lactamase in carbapenem resistance in clinical isolates of Pseudomonas aeruginosa

Imipenem-rcsistant clinical isolates of Pseudomonas aeruginosa were divided into two categories: (i) isolates that were moderately resistant to imipenem (MIC 6-25 mg/L) that produced trace amounts of protein D2 detected with immuneblotting using anti-protein D2 antibody, but not when stained with Coomassie blue and had inducible class 1 /f-lactamase expression; (ii) isolates that were highly resistant to several /Mactams, including meropenem, with no protein D2 by staining or immunoblotting and had stably derepressed /Mactamase. Laboratory strains were isolated and analyzed: (i) mutants lacking protein D2, or (ii) lacking protein D2 and producing stably derepressed /J-lactamase with carbapenem resistance similar to the clinical isolates, (iii) mutants producing undetectable 0-lactamasc which were fourfold more susceptible to imipenem than the mutant producing stably derepressed /J-lactamase or the strain with inducible /J-lactamase. These data suggests that /Mactamase and outer membrane permeability govern meropenem-resistance in P. aeruginosa

Correlated Prompt Fission Data in Transport Simulations

Detailed information on the fission process can be inferred from the observation, modeling and theoretical understanding of prompt fission neutron and $\gamma$-ray~observables. Beyond simple average quantities, the study of distributions and correlations in prompt data, e.g., multiplicity-dependent neutron and \gray~spectra, angular distributions of the emitted particles, $n$-$n$, $n$-$\gamma$, and $\gamma$-$\gamma$~correlations, can place stringent constraints on fission models and parameters that would otherwise be free to be tuned separately to represent individual fission observables. The FREYA~and CGMF~codes have been developed to follow the sequential emissions of prompt neutrons and $\gamma$-rays~from the initial excited fission fragments produced right after scission. Both codes implement Monte Carlo techniques to sample initial fission fragment configurations in mass, charge and kinetic energy and sample probabilities of neutron and $\gamma$~emission at each stage of the decay. This approach naturally leads to using simple but powerful statistical techniques to infer distributions and correlations among many observables and model parameters. The comparison of model calculations with experimental data provides a rich arena for testing various nuclear physics models such as those related to the nuclear structure and level densities of neutron-rich nuclei, the $\gamma$-ray~strength functions of dipole and quadrupole transitions, the mechanism for dividing the excitation energy between the two nascent fragments near scission, and the mechanisms behind the production of angular momentum in the fragments, etc. Beyond the obvious interest from a fundamental physics point of view, such studies are also important for addressing data needs in various nuclear applications. (See text for full abstract.)Comment: 39 pages, 57 figure files, published in Eur. Phys. J. A, reference added this versio

Drug review process advancement and required manufacturer and contract research oraganization responses

\ua9 2024 The Japanese Society of Toxicologic Pathology.The United States Senate passed the “FDA Modernization Act 2.0.” on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient safety. Nonetheless, society is becoming increasingly opposed to animal testing, and efforts will be made to use fewer animals and conduct fewer animal tests as a natural and reasonable response. These changes eventually alter the shape of new drug applications. Based on the assumption that fewer animal tests will be conducted or fewer animals will be used in testing, this study explored bioinformatics and new technologies as alternatives to compensate for reduced information and provide a picture of how future new drug applications may look. The authors also discuss the directions that pharmaceutical companies and nonclinical contract research organizations should adopt to promote the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibitions

コウトウ キョウイク ト ショウガイ キョウイク オ カンガエル International Conference : チイキ シャカイジン オ カツヨウ シタ キョウヨウ キョウイク ノ イッカン トシテノ ニッチュウカン コウリュウ

平成20年度採択の質の高い大学教育改革プログラム「地域社会人を活用した教養教育」では、 地域社会人の勉学に対する高いモチベーションを、共に学ぶ学生が、自ら感じて学び取ることを目的としている。この取り組みを発展させていくために、取り組みに関係する近接する諸外国との意見交換が考えられる。この3カ国では、少子高齢化の問題に関しても共通する課題であり、大学教育に関する課題に関しても共通点が多い。本稿では、今回徳島大学全学共通教育学びのコミュニティー主催で開催した「高等教育と生涯教育に関する国際会議」の概要とその結果得られた成果について様々な角度から考察する

Neutrophil C5a receptor and the outcome in a rat model of sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154259/1/fsb2fj030009fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154259/2/fsb2fj030009fje-sup-0001.pd

Forkhead Transcription Factors (FoxOs) Promote Apoptosis of Insulin-Resistant Macrophages During Cholesterol-Induced Endoplasmic Reticulum Stress

OBJECTIVE—Endoplasmic reticulum stress increases macrophage apoptosis, contributing to the complications of atherosclerosis. Insulin-resistant macrophages are more susceptible to endoplasmic reticulum stress–associated apoptosis probably contributing to macrophage death and necrotic core formation in atherosclerotic plaques in type 2 diabetes. However, the molecular mechanisms of increased apoptosis in insulin-resistant macrophages remain unclear

Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients

AIMS: The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. However, the association of the AR gene with diabetic macroangiopathy has not been investigated. Therefore, the present study was conducted to determine whether genetic variations of AR may determine susceptibility to diabetic macroangiopathy. METHODS: There were 378 Type 2 diabetic patients enrolled in this study. A single nucleotide polymorphism in the promoter region (C-106T) was genotyped and the AR protein content of erythrocytes measured by ELISA. RESULTS: There were no significant differences in genotypic or allelic distribution in patients with or without ischaemic heart diseases, but there was a significant increase in the frequency of the CT + TT genotype and T allele in patients with stroke (P = 0.019 and P = 0.012). The erythrocyte AR protein content was increased in patients with the CT and TT genotype compared with those with the CC genotype. After adjustment for age, duration of diabetes, body mass index, systolic blood pressure, HbA(1c), and serum creatinine, triglycerides, and total cholesterol in multivariate logistic-regression models, the association between this AR genotype and stroke remained significant. CONCLUSIONS: Our results suggest that the CT or TT genotype of the AR gene might be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This observation might contribute to the development of strategies for the prevention of stroke in Type 2 diabetic patients

NKT Cell Stimulation with α-Galactosylceramide Results in a Block of Th17 Differentiation after Intranasal Immunization in Mice

In a previous study we demonstrated that intranasal (i.n.) vaccination promotes a Th17 biased immune response. Here, we show that co-administration of a pegylated derivative of α-galactosylceramide (αGCPEG) with an antigen, even in the presence of Th17-polarizing compounds, results in a strong blocking of Th17 differentiation. Additional studies demonstrated that this phenomenon is specifically dependent on soluble factors, like IL-4 and IFNγ, which are produced by NKT cells. Even NK1.1 negative NKT cells, which by themselves produce IL-17A, are able to block Th17 differentiation. It follows that the use of αGCPEG as adjuvant would enable to tailor Th17 responses, according to the specific clinical needs. This knowledge expands our understanding of the role played by NKT cells in overall control of the cytokine microenvironment, as well as in the overall shaping of adaptive immune responses