Oceanic Boundary Currents

Measurements of oceanic boundary currents for integral quantities such as heat and freshwater transports are very important for studying their long-term impacts on the global climate. There are a variety of boundary currents, including surface, intermediate and deep boundary currents on both the western and eastern sides of ocean basins. The dynamics and physics of these boundary currents are different, as are the ways of monitoring them. Here, we choose to explore the strategies adopted for observing four representative boundary current systems which have been the subject of detailed studies in recent years: the Kuroshio; the East Australian Current; the Indonesian Throughflow; and the low-latitude boundary current System of the Atlantic. The transport of the Kuroshio south of Japan has been monitored using satellite altimeter data in conjunction with an empirical relation between the transport and sea surface height difference across the stream. Monitoring the transport of the East Australian Current has been achieved by repeated high-resolution expendable bathythermograph (XBT) and/or conductivity-temperature-depth profiler transects maintained at several locations, supplemented with satellite altimeter data. Repeated XBT transects have also been used to monitor transport of the Indonesian Throughflow, in association with current meter and other instrumental estimations of transport through a few major throughflow straits. Finally, the complicated flow field of the low-latitude boundary current system of the Atlantic has been revealed using neutrally buoyant floats, moored current meters and hydrographic observations. The survey will be continued using further advanced observation technologies

Molecular cloning of a cDNA encoding human ribosomal protein L39

A cDNA clone encoding a human ribosomal protein L39 (hRPL39) was isolated through a random cDNA sequencing approach to a cDNA library constructed from a human colon carcinoma cell line of COLO 205. Although levels of hRPL39 mRNA were different in several cell lines including carcinoma cell lines from different tissues, they were shown not to be cell cycle-dependent in a human fibroblast cell line of TIG-1

Time-Dependent Changes in Risk of Progression During Use of Bevacizumab for Ovarian Cancer

卵巣がんに対する分子標的薬「ベバシズマブ」の効果を解析 投与終了後に悪化リスクが高まることを確認、最適な投与法を提案. 京都大学プレスリリース. 2023-08-03.[Importance] Although bevacizumab has been used in the treatment of ovarian cancer, its optimal use is unknown. [Objective] To investigate time-dependent changes in the outcomes of bevacizumab therapy. [Design, Setting, and Participants] This cohort study was conducted using published data from 7 previous randomized phase 3 clinical trials with bevacizumab (ICON7, GOG-0218, BOOST, GOG-0213, OCEANS, AURERIA, and MITO16B) from January 10 to January 31, 2023. From 2 ancillary analyses of the ICON7 trial with individual patient data and tumor gene expression profiles, an ICON7-A cohort was generated comprising 745 cases. From other studies, published Kaplan-Meier curves were graphically analyzed. [Exposures] Bevacizumab treatment vs placebo or no treatment. [Main Outcomes and Measures] Restricted mean survival time and relative risk of progression at a given time point between bevacizumab treatment and control groups. [Results] In the ICON7-A cohort (n = 745), restricted mean survival analysis showed that bevacizumab treatment (n = 384) had significantly better progression-free survival (PFS) than the control (n = 361) before bevacizumab discontinuation (restricted mean survival time ratio, 1.08; 95% CI, 1.05-1.11; P < .001), but had significantly worse PFS after bevacizumab discontinuation (0.79; 95% CI, 0.69-0.90; P < .001), showing rebound. In a post hoc analysis, the rebound was similarly observed both in homologous recombination deficiency (HRD) (before, 1.05; 95% CI, 1.02-1.09; P < .001; after, 0.79; 95% CI, 0.63-0.98; P = .04) and non-HRD tumors (before, 1.08; 95% CI, 1.03-1.15; P < .001; after, 0.71; 95% CI, 0.56-0.90; P < .001) of the serous subtype, but not in the nonserous subtype (before, 1.11; 95% CI, 1.05-1.18; P < .001; after, 0.94; 95% CI, 0.78-1.15; P = .57). In Kaplan-Meier curve image–based analysis, the trend of rebound effect was consistently observed in the overall ICON7 and GOG-0218 cohorts and their subgroups stratified by prognostic factors, homologous recombination–associated mutations, and chemotherapy sensitivity. In contrast, no such trend was observed in the studies GOG-0213, OCEANS, AURERIA, and MITO16B, in which patients who experienced relapse received bevacizumab until progression. [Conclusions and Relevance] In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment, bevacizumab may be more beneficial in patients with a shorter prognosis who are less likely to experience the rebound outcome

New mechanism leading to alleviation of salt-sensitive hypertension by a powerful angiotensin receptor blocker, azilsartan

Hypertension is one of the most life-threatening health problems in the modern world. Particularly, salt-sensitive hypertension is often associated with cardiovascular disease and defects in the circadian rhythm of the blood pressure. To date, the effects of angiotensin receptor blocker (ARB) against salt sensitivity and the blood pressure’s circadian rhythm have been obscure. A strong ARB, azilsartan, was previously reported to improve the circadian rhythm of blood pressure in hypertensive patients. In a recently published study, we investigated the mechanism by which azilsartan brought about this reaction. We speculated that azilsartan modulated sodium transporters located in the renal tubules because the circadian rhythm of blood pressure is linked to salt handling in the kidney. We discovered that one sodium transporter, NHE3 protein, in the proximal tubules was greatly attenuated in the kidneys of 5/6 nephrectomized mice that had been treated with azilsartan, although the expression of other sodium transporter proteins remained unchanged. The genetic expression of NHE3, however, was not changed by azilsartan. In a subsequent in vitro study using OKP cells, we found that NHE3 protein reduction was induced by enhanced protein degradation by proteasomes, not lysosomes, leading to enhanced sodium excretion. It is suggested that diminished salt sensitivity in the 5/6 nephrectomized mice treated with azilsartan was due to a change in sodium handling induced by the reduction of NHE3 protein in the proximal tubules. These mechanisms underlying the decreased salt sensitivity by azilsartan treatment may lead to totally new drug discoveries