Comparing α-carbanion-stabilizing ability of substituents using the Brook rearrangement

The α-carbanion-stabilizing ability of the phenylthio and trimethylsilyl groups was compared based on the relative rate of the base-catalyzed Brook rearrangement of the β-substituted α-silylallylalcohol

Formação de clamidósporos pela fase micelial do Paracoccidioides brasiliensis

To investigate the role of some adverse environmental conditions in chlamy-dospore formation by the mycelial form of P. brasiliensis, we cultured four P. brasiliensis isolates (18, Bt4, 1183, Pb9) at 25°C within solid agar medium either rich or poor in nutrients. Isolates 18 and 1183 were also cultured under anaerobiosis in a nitrogen atmosphere. Isolate 18 produced great number of terminal and intercalary chlamydospore after 7-10 days of culture in a medium poor in nutrients (2% agar with 0.1% dextrose and polypepton). The three other isolates also produced chlamydospores under the same conditions, but in lower numbers. Chlamydospore production by isolate 18 was abolished when the fungus was cultured in two agar media rich in nutrients (brain heart infusion and potato dextrose agar). Anaerobic incubation of isolate 18 under an atmosphere of N2 showed small mycelial outgrowth with numerous chlamydospores. At the electron microscopical level, the chlamydospores showed one or various nuclei and numerous mitochondria, indicating great potential for further development. Accordingly, chlamydospores produced multiple budding after only 24 h incubation at 35°C. The results demonstrate that under adverse environmental conditions P. brasiliensis mycelial form produces chlamydospores within a short period of time.O papel do conteúdo nutritivo do meio de cultura e de oxigênio na produção de clamidósporos pela fase micelial do Paracoccidioides brasiliensis foi investigado. Quatro cepas do fungo (18, Bt4, 1183, Pb9) foram cultivadas, a 25°C, em meio sólido rico e pobre em nutrientes. As cepas 18 e 1183 foram também cultivadas em anerobiose em atmosfera de nitrogênio. A cepa 18 produziu grande número de clamidósporos terminais e intercalares após 7-10 dias de cultura em meio sólido pobre em nutrientes (agar 2%, com dextrose e polipeptona 0,1%). As outras três cepas produziram número significativamente menor de esporos. A cepa 18 não produziu clamidósporos quando cultivada em dois meios ricos em nutrientes (infusão de cérebro e coração, e agar dextrose de batata). A incubação anaeróbica da cepa 18 em atmosfera de nitrogênio apresentou pequeno crescimento micelial com a presença de numerosos clamidósporos. À nivel ultraestrutural, os clamidósporos apresentaram um ou mais núcleos e numerosas mitocôndrias, indicativos de potencial para posterior desenvolvimento. Assim, os esporos produziram gemulação múltipla 1 dia após incubação a 35°C. Os resultados demonstraram que, sob condições ambientais adversas, a fase micelial do P. brasiliensis produz clamidósporos em curto período de tempo. É possível que o fungo encontre condições semelhantes no solo, produzindo os esporos, que poderiam desempenhar papel na propagação da paracoccidioidomicose

Recent trend of research on the nongenotoxic mechanisms of chemical carcinogenesis

本総説は,筆者らが進めている｢低線量放射線の健康への影響と医療への応用｣に関する研究に資するために調査した,化学発がんの非遺伝毒性的メカニズムの解明に関する最近の動向の概要についてまとめたものである｡即ち,非遺伝毒性的発がんにおける細胞増殖,シトクロムP450誘導,酸化的ストレス,および遺伝子発現のそれぞれの役割,並びに量的な応答性について言及した｡また,後成的発がんにおけるアポトーシス,およびギャップ結合による情報伝達のそれぞれの役割についても触れた｡その結果,非遺伝毒性的な発がん物質の作用の様式とメカニズムやこれによる後成的な影響などについては解明さ れつつあり,特に,これらの発がん物質がゲノムDNAに対し直接的な相互作用,突然変異,修飾などを行う発がん物質とは機能的に異なった作用をすることが明らかになった｡また,これらは放射線発がんなど低線量放射線の健康への影響などについて研究する上で,重要な知見となっていることもわかった。To elucidate the health effects by low dose radiation, we reviewed the recent trend of research on the epigenetic mechanisms of chemical carcinogenesis. The following view were obtained. It has become apparent that chemical and physical agents that induce cancer may do so through different cellular and molecular mechanisms. Investigators, recognizing the apparent differences in the ways compounds participate in the carcinogenesis process, coined the phrases "genotoxic" and "epigenetic" in describing activities of chemicals and physical agents that induced cancer. The term "nongenotoxic" has to some extent replaced "epigenetic" and thus, classification of chemical carcinogens has been frequently delegated to either the genotoxic or nongenotoxic categories. Moreover, while much work remains in the understanding of the modes and mechanisms of action of nongenotoxic carcinogens and the epigenetic effects of these agents, it is apparent that this category of chemicals are functionally different than those compounds which directly interact, mutate, and modify genomic DNA

Essential pre-treatment imaging examinations in patients with endoscopically-diagnosed early gastric cancer

<p>Abstract</p> <p>Background</p> <p>There have been no reports discussing which imaging procedures are truly necessary before treatment of endoscopically-diagnosed early gastric cancer (eEGC). The aim of this pilot study was to show which imaging examinations are essential to select indicated treatment or appropriate strategy in patients with eEGC.</p> <p>Methods</p> <p>In 140 consecutive patients (95 men, 45 women; age, 66.4 +/- 11.3 years [mean +/- standard deviation], range, 33-90) with eEGC which were diagnosed during two years, the pre-treatment results of ultrasonography (US) and contrast-enhanced computed tomography (CT) of the abdomen, barium enema (BE) and chest radiography (CR) were retrospectively reviewed. Useful findings that might affect indication or strategy were evaluated.</p> <p>Results</p> <p>US demonstrated useful findings in 13 of 140 patients (9.3%): biliary tract stones (n = 11) and other malignant tumors (n = 2). Only one useful finding was demonstrated on CT (pancreatic intraductal papillary mucinous tumor) but not on US (0.7%; 95% confidential interval [CI], 2.1%). BE demonstrated colorectal carcinomas in six patients and polyps in 10 patients, altering treatment strategy (11.4%; 95%CI, 6.1-16.7%). Of these, only two colorectal carcinomas were detected on CT. CR showed three relevant findings (2.1%): pulmonary carcinoma (n = 1) and cardiomegaly (n = 2). Seventy-nine patients (56%) were treated surgically and 56 patients were treated by endoscopic intervention. The remaining five patients received no treatment due to various reasons.</p> <p>Conclusions</p> <p>US, BE and CR may be essential as pre-treatment imaging examinations because they occasionally detect findings which affect treatment indication and strategy, although abdominal contrast-enhanced CT rarely provide additional information.</p

Candida albicans

Genotypes of Candida spp. isolated from exhalation of 20 dolphins, 11 water samples from captive pools, and 24 oral cavities of staff members in an aquarium using a combination of multiple drug resistance 1 gene (MDR1) and the internal transcribed spacer (ITS) 1 5.8s-ITS 2 regions of ribosomal RNA gene (ITS rDNA) sequences were studied. The holding ratios of the dolphins, captive pools, and staff members were 70, 90, and 29%, respectively. Isolated pathogenic yeast species common to the dolphins and environments were Candida albicans and C. tropicalis. Identical genotypes in both Candida spp. based on the combination of MDR1 and ITSrDNA were found in some dolphins, between a dolphin and a staff, among dolphins and environments, and among environments. The results indicated the diffusion and exchange of pathogenic yeasts at the aquarium among dolphins and environments. The isolates at the aquarium showed higher rates of resistance to azole antifungals compared to reference isolates

Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero

Newly identified tissue-resident vascular precursor cells are recruited into growing vessels and contribute to vasculogenesis in adult mice

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target