2,3-Dimeth­oxy-5,12-tetra­cenequinone

The mol­ecule of the title compound, C20H14O4, is approximately planar [maximum deviation 0.168 (2) Å]. The two meth­oxy groups are slightly twisted relative to the plane of the 5,12-tetra­cenequinone system, with twist angles of 3.3 (3) and 5.6 (2)°. All O atoms are involved in intermolecular C—H⋯O inter­actions and the mol­ecules are arranged into slipped face-to-face stacks along the b axis via π–π inter­actions with an inter­planar distance of 3.407 (2) Å

The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice

Both TDP-43 pathology and failure of RNA editing of AMPA receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS). AR2 mice, in which an RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is conditionally knocked out in the motor neurons, exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons through a Ca2+-permeable AMPA receptor-mediated mechanism. Therefore, amelioration of the increased Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here, we showed that orally administered perampanel, a selective, non-competitive AMPA receptor antagonist significantly prevented the progression of the ALS phenotype and normalized the TDP-43 pathology-associated death of motor neurons in the AR2 mice. Given that perampanel is an approved anti-epileptic drug, perampanel is a potential candidate ALS drug worthy of a clinical trial.UTokyo Research掲載「筋萎縮性側索硬化症の治療法に向けて」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/finding-a-treatment-for-als.htmlUTokyo Research "Finding a treatment for ALS" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/finding-a-treatment-for-als.htm

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings

Had COVID-19 spread in the community before the first confirmed case in Nagasaki, Japan?

This retrospective study evaluated stored nasopharyngeal swab samples from Japanese patients with influenza-like illness during the 2019/2020 season. We aimed to determine whether COVID-19 had spread in the community before the first confirmed case. The period of influenza season during 2019/2020 in Nagasaki was shorter than in previous influenza seasons. When the first COVID-19 case was reported in Nagasaki prefecture, the number of influenza cases were very low. No positive results for SARS-CoV-2 were detected in 182 samples that were obtained from adult outpatients. Our results revealed no large-scale spread of COVID-19 in the community before the first confirmed case

Fluoroquinolone resistance in extended-spectrum β-lactamase-producing Klebsiella pneumoniae in a Japanese tertiary hospital: silent shifting to CTX-M-15-producing K. pneumoniae

Purpose. Fluoroquinolone resistance (FQ-r) in extended-spectrum β-lactamase (ESBL) producers is an urgent health concern in countries where ESBL-producing K. pneumoniae (ESBL-Kpn) is prevalent. We investigated FQ-r in Japan where ESBL-Kpn is less prevalent. Methodology. Clinical ESBL-Kpn isolates from 2011 to 2013 were collected in Nagasaki University Hospital. The ESBL genotypes included CTX-M-15, and the mechanisms of FQ-r through plasmid-mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining regions (QRDRs) were examined. Clonality was analysed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and multi-locus sequence typing was performed on selected isolates. Results/Key findings. Thirty ESBL-Kpn isolates, including seven levofloxacin-resistant isolates, were obtained from different patients. An increase in CTX-M-15-producing strains was observed during the study period (0/11 in 2011, 3/8 in 2012, and 5/11 in 2013). PMQR was detected in 53.3?% of the isolates and aac-(6′)-Ib-cr was the most common (36.7?%). ST15 was observed in 60.0?% of the isolates, and for the most predominant ERIC-PCR profiles, 62.5?% of the isolates possessed the CTX-M-15 genotype and 71.4?% were levofloxacin-resistant. Levofloxacin-resistance was significantly more common in CTX-M-15 isolates (62.5?%) compared to non-CTX-M-15 isolates (9.1?%). Three QRDR mutations and aac(6′)-Ib-cr, but not qnrB and qnrS, were significantly enriched in the CTX-M-15 isolates (100.0?%) compared to the non-CTX-M-15 isolates (13.6?%). Conclusion. Cumulatively, these results indicate that the epidemic strain, the CTX-M-15-producing K. pneumoniae ST15, is covertly spreading even when ESBL producers are not prevalent. Monitoring these epidemic strains and ESBLs in general is important for quickly identifying health crises and minimizing future risks from FQ-r ESBL-Kpn

A practical device for pinpoint delivery of molecules into multiple neurons in culture

We have developed a device for pinpoint delivery of chemicals, proteins, and nucleic acids into cultured cells. The principle underlying the technique is the flow of molecules from the culture medium into cells through a rupture in the plasma membrane made by a needle puncture. DNA transfection is achieved by stabbing the needle tip into the nucleus. The CellBee device can be attached to any inverted microscope, and molecular delivery can be coupled with conventional live cell imaging. Because the position of the needle relative to the targeted cultured cells is computer-controlled, efficient delivery of molecules such as rhodamine into as many as 100 HeLa cells can be completed in 10 min. Moreover, specific target cells within a single dish can be transfected with multiple DNA constructs by simple changes of culture medium containing different plasmids. In addition, the nano-sized needle tip enables gentle molecular delivery, minimizing cell damage. This method permits DNA transfection into specific hippocampal neurons without disturbing neuronal circuitry established in culture