Concentration dependence of thermal isomerization process of methyl orange in ethanol

The thermal isomerization (TI) rates of methyl orange (MO) and 4-dimethylaminoazobenzene (DMAAB) in ethanol (EtOH) are measured. Usually TI rates of azobenzene dyes are known to be concentration independent. However, the TI rate of MO showed a concentration dependence whereas that of DMAAB did not. The TI rate of DMAAB in EtOH became larger by the addition of alkali halide. This phenomenon is caused mainly by the interaction between DMAAB and cation. MO is a derivative of DMAAB in which one end of the azobenzene is substituted by a SO3-Na+ group. The interaction with the dissociated Na+ ion is considered to be an origin of the concentration dependence of the TI rate of MO

BLM–DNA2–RPA–MRN and EXO1–BLM–RPA–MRN constitute two DNA end resection machineries for human DNA break repair

Repair of dsDNA breaks requires processing to produce 3′-terminated ssDNA. We biochemically reconstituted DNA end resection using purified human proteins: Bloom helicase (BLM); DNA2 helicase/nuclease; Exonuclease 1 (EXO1); the complex comprising MRE11, RAD50, and NBS1 (MRN); and Replication protein A (RPA). Resection occurs via two routes. In one, BLM and DNA2 physically and specifically interact to resect DNA in a process that is ATP-dependent and requires BLM helicase and DNA2 nuclease functions. RPA is essential for both DNA unwinding by BLM and enforcing 5′ → 3′ resection polarity by DNA2. MRN accelerates processing by recruiting BLM to the end. In the other, EXO1 resects the DNA and is stimulated by BLM, MRN, and RPA. BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. Our results establish two of the core machineries that initiate recombinational DNA repair in human cells

Development and application of a simple LC-MS method for the determination of plasma maraviroc concentrations

Maraviroc is an orally available antagonist of the CCR5 chemokine receptor, which acts as a human immunodeficiency virus type 1 (HIV-1) coreceptor. Binding of maraviroc to this receptor blocks HIV-1 attachment to the coreceptor and prevents HIV-1 from entering host cells.Maraviroc does not require intracellular processing to exert this activity. Drug interaction studies have shown changes in maraviroc exposure when given with other anti-HIV medications, and thus quantification of maraviroc in human plasma is important to manage drug interactions and to evaluate the relationship between plasma concentrations and treatment response. We developed a conventional LCMS method for determining plasma maraviroc concentrations, validated by estimating precision and accuracy for inter- and intraday analysis in the concentration range of 0.011-2.188g/ml. The calibration curve was linear within this range. The average accuracy ranged from 92.7% to 99.7%, while the relative standard deviations of both interand intraday assays were less than 7.1%. Recovery of maraviroc exceeded 86.7%. Our LCMS method provides a conventional, accurate and precise way to determine the maraviroc concentration in human plasma. This method enables dose adjustment based on monitoring plasma maraviroc concentrations and permits management of drug interactions and toxicity

The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects

SummaryIntracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) mutant. β-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the β-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis

ウマ ノ ガイボウ ニ タイスル ヒト ノ シカク ニンチ

本研究は,動物との相互関係における人の視覚認知に着目し,視線計測装置を用いて馬を観察した際の人の視線追従(注視部位,注視回数,注視時間)ならびに瞳孔径の変化を定量化した。さらに観察者の性格特性や馬に対する印象と視線との関連性を考察することを目的とした。得られたデータから,人の性格傾向において,外向性が高いほど肢・尻の部位に対し,また神経症傾向が高いほど,首・肩・胸の部位に対する注視回数や注視時間が低かった。特に神経症傾向が高い場合,馬の顔に視線が集まるといった,観察者の性格特性と注視部位に関連が認められた。また馬に対する恐怖感は,馬の外貌の中でも脚部から影響を受けると考えられた。さらに乗馬経験および動物の飼育経験と馬の顔への注視回数・時間に有意な正の相関が認められた。これらの結果から,人が動物との関係をもつ場合,アイコンタクトをはじめとした人同士のコミュニケーション方法を動物に対しても同様に適用していると考えられた。これらの視線解析を中心とした本研究の結果は,馬との相互関係から得られる精神的効果,また現在まで多く報告されている自閉症をはじめとしたコミュニケーションに関する障碍に対する動物介在療法・活動・教育の実施内容を支持するものである。This study was conducted to investigate the visual tracking processes and pupil diameter changes of subjects while observing horses, and to analyze the relationship between the personality characteristics of these subjects and their impressions about horses. Mobile Eye Tracking Product was used to measure which part of the horse\u27s body the subjects were observing more frequently than the other parts. The observed body parts of the horse were categorized into four areas : "face", "neck, shoulders, chest", "abdomen, back", and "extremities, buttocks". A quantitative analysis was conducted based on observation frequency and time, as well as pupil diameter, while tracking the observation of each of the above-mentioned four categorized body parts of the horse. The personality of each subject and his/her impressions about the horse were digitized, and this individual trait and the result of the visual trait analysis were compared and examined. Those data indicate that there is a correlation among personality characteristics of the subjects, their impressions about horses, and their close observations of the body parts of the horses. On the one hand, feelings of fear seem to be influenced by the appearance of the horses\u27 extremities, and on the other hand, there is a positive correlation between horseback riding and nurturing experiences, and the frequency and time of observing the face of the horse. The behavior of making eye contact to establish communication between humans is also applied for establishing relationships between humans and animals. The results of this study including the visual tracking analysis support the notion of the beneficial psychological effects obtained by the mutual relationship between humans and horses in the fields of education, various activities, and animal assisted therapy for persons suffering from communication disorders such as autism

RAD50 and NBS1 form a stable complex functional in DNA binding and tethering

The RAD50/MRE11/NBS1 protein complex (RMN) plays an essential role during the early steps of DNA double-strand break (DSB) repair by homologous recombination. Previous data suggest that one important role for RMN in DSB repair is to provide a link between DNA ends. The striking architecture of the complex, a globular domain from which two extended coiled coils protrude, is essential for this function. Due to its DNA-binding activity, ability to form dimers and interact with both RAD50 and NBS1, MRE11 is considered to be crucial for formation and function of RMN. Here, we show the successful expression and purification of a stable complex containing only RAD50 and NBS1 (RN). The characteristic architecture of the complex was not affected by absence of MRE11. Although MRE11 is a DNA-binding protein it was not required for DNA binding per se or DNA-tethering activity of the complex. The stoichiometry of NBS1 in RMN and RN complexes was estimated by SFM-based volume analysis. These data show that in vitro, R, M and N form a variety of stable complexes with variable subunit composition and stoichiometry, which may be physiologically relevant in different aspects of RMN function

Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.Tomofuji Yoshihiko, Kishikawa Toshihiro, Sonehara Kyuto, et al. Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population. Cell Reports 42, 113324 (2023); https://doi.org/10.1016/j.celrep.2023.113324

Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study

Abstract Objective: Resting energy expenditure (REE) decreases if there is reduced energy intake and body weight (BW). The decrease in REE could make it difficult for patients with obesity to maintain decreased BW. This study aimed to investigate the correlation among changes in REE, energy intake, and BW during the weight loss process in patients with obesity. Materials and methods: We conducted a retrospective cohort study of patients hospitalized for the treatment of obesity in Japan. Patients received fully controlled diet during hospitalization and performed exercises if able. REE was measured once a week using a hand-held indirect calorimetry. Energy intake was determined by actual dietary intake. Results: Of 44 inpatients with obesity, 17 were included in the analysis. Their BW decreased significantly after 1 week (−4.7 ± 2.0 kg, P < 0.001) and 2 weeks (−5.7 ± 2.2 kg, P < 0.001). The change in REE after 1 and 2 weeks was positively correlated with the energy intake/energy expenditure ratio (r = 0.66, P = 0.004 at 1 week, r = 0.71, P = 0.002 at 2 weeks). Using a regression equation (y = 0.5257x – 43.579), if the energy intake/energy expenditure ratio within the second week was 82.9%, the REE after 2 weeks was similar to the baseline level. There was no significant correlation between the change in REE and BW. Conclusions: Our data suggest that changes in REE depend on energy intake/energy expenditure ratio and that the decrease in REE can be minimized by matching energy intake to energy expenditure, even during the weight loss process