Bubbly Flows through a Convergent-Divergent Nozzle

Characteristics of bubbly flow with a small void fraction through a vertical, two-dimensional, converging-diverging nozzle are investigated experimentally and numerically. Emphasis is placed on the mechanism for large velocity slip near the nozzle throat, where the pressure gradient is very large. Bubble velocities are measured by taking double-exposure photographs with stroboscopic light sources having a flash duration of a few μ sec. The pressure distribution of the mixture along the nozzle axis is measured by semiconductor pressure transducers. The local liquid velocity is determined through continuity equations of gas and liquid in conjunction with the measured data of pressure distribution and experimental conditions at the nozzle inlet and exit. The power spectrum density of the pressure fluctuations is measured to investigate some instabilty of the bubbly flow, which is believed to be inherent to the velocity slip. It is proved that the numerical results using Wijngaarden's model equations agree well with the experiments. The characteristics of flow instability are explained according to the theoretical predictions of Morioka et al

Effective and Steady Differentiation of a Clonal Derivative of P19CL6 Embryonal Carcinoma Cell Line into Beating Cardiomyocytes

The P19CL6 cell line is a useful model to study cardiac differentiation in vitro. However, large variations were noticed in the differentiation rates among previous reports as well as our individual experiments. To overcome the unstable differentiation, we established P19CL6-A1, a new clonal derivative of P19CL6 that could differentiate into cardiomyocytes more efficiently and stably than the parent using the double stimulation with 5-Aza and DMSO based on the previous report. We also introduced a new software, Visorhythm, that can analyze the temporal variations in the beating rhythms and can chart correlograms displaying the oscillated rhythms. Using P19CL6-A1-derived cardiomyocytes and the software, we demonstrated that the correlograms could clearly display the enhancement of beating rates by cardiotonic reagents. These indicate that a combination of P19CL6-A1 and Visorhythm is a useful tool that can provide invaluable assistance in inotropic drug discovery, drug screening, and toxicity testing

Characteristics and clustering of human ribosomal protein genes

BACKGROUND: The ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs). The control mechanisms of gene expression and the functions of RPs are believed to be identical. Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism. RESULTS: We systematically analyzed the homogeneity and heterogeneity of RP genes on the basis of their expression profiles, promoter structures, encoded amino acid compositions, and codon compositions. The results revealed that (1) most RP genes are coordinately expressed at the mRNA level, with higher signals in the spleen, lymph node dissection (LND), and fetal brain. However, 17 genes, including the P protein genes (RPLP0, RPLP1, RPLP2), are expressed in a tissue-specific manner. (2) Most promoters have GC boxes and possible binding sites for nuclear respiratory factor 2, Yin and Yang 1, and/or activator protein 1. However, they do not have canonical TATA boxes. (3) Analysis of the amino acid composition of the encoded proteins indicated a high lysine and arginine content. (4) The major RP genes exhibit a characteristic synonymous codon composition with high rates of G or C in the third-codon position and a high content of AAG, CAG, ATC, GAG, CAC, and CTG. CONCLUSION: Eleven of the RP genes are still identified as being unique and did not exhibit at least some of the above characteristics, indicating that they may have unknown functions not present in other RP genes. Furthermore, we found sequences conserved between human and mouse genes around the transcription start sites and in the intronic regions. This study suggests certain overall trends and characteristic features of human RP genes

Studies on Alterations in Acid Phosphatase Activity, Body Weight and Ultrastructure of Adult Angiostrongylus cantonensis in Rats Treated with Flubendazole at a Subcurative Dose

Physiological effects of flubendazole on adult Angiostrongylus cantonensis were studied. Administration of flubendazole for 3 consecutive days (48-50 days post-infection) at 10 mg/kg/day did not affect the number of worms of and weight of adult female A. cantonensis recovered from rats 16 hr after termination of medication while it lowered the phosphatase activity by the intact worms. The possible modes of action of the drug were discussed together with electron-microscopic observation of the body wall of the worms recovered from the treated and non-treated rats

Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)­(2,4′-bipyridin-3-yl)­methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies

Impaired Anaphylactic Responses with Intact Sensitivity to Endotoxin in Mice Lacking a Platelet-activating Factor Receptor

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor–deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock

Sex-dependent regulation of vertebrate somatic growth and aging by germ cells

Abe K., Ino H., Niwa T., et al. Sex-dependent regulation of vertebrate somatic growth and aging by germ cells. Science Advances 10, eadi1621 (2024); https://doi.org/10.1126/sciadv.adi1621.The function of germ cells in somatic growth and aging has been demonstrated in invertebrate models but remains unclear in vertebrates. We demonstrated sex-dependent somatic regulation by germ cells in the short-lived vertebrate model Nothobranchius furzeri. In females, germ cell removal shortened life span, decreased estrogen, and increased insulin-like growth factor 1 (IGF-1) signaling. In contrast, germ cell removal in males improved their health with increased vitamin D signaling. Body size increased in both sexes but was caused by different signaling pathways, i.e., IGF-1 and vitamin D in females and males, respectively. Thus, vertebrate germ cells regulate somatic growth and aging through different pathways of the endocrine system, depending on the sex, which may underlie the sexual difference in reproductive strategies

トクベツ ヨウゴ ロウジン ホーム デ ハタラク ケア ワーカー ト カンゴシ ノ シュウマツキ ケア コウドウ ノ ブンセキ リョウ ショクシュ ノ センモンセイ ニ モトヅク キョウドウ ノ カノウセイ

在宅生活の継続と介護費用の伸びを抑制する必要性から， 在宅系介護サービスの充実が図られてきたが， 療養病床の削減や女性の社会進出など社会的条件の変化により， 施設サービスへの需要も大きく， そこでの終末期ケアの充実が課題となっている． 筆者らは， 大阪府下の 41 特養に勤務するケアワーカー 255 名， 看護師 84 名の協力を得て， 終末期ケア行動の内容を明らかにするとともに， 両職種の協働の在り方について考察した． その結果， 『医療処置に関するケア （第 1 因子）』 『利用者の意思の尊重と家族への説明に関するケア （第 2 因子）』 『生活支援に関するケア （第 3 因子）』 『病状把握と看取りケアに関するケア （第 4 因子）』 という終末期ケア行動を構成する 4 つの因子が明らかになった． 各因子をさらに分析した結果， 第 1・ 4 因子については看護師が， 第 2・ 3 因子についてはケアワーカーが主として担うことがよりよい協働に寄与するものと考える