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Studies have found that blood flow to the renal medulla is an important determinant of pressure-natriuresis and the long-term regulation of arterial pressure. First, a brief review of methods developed enabling the study of the medullary circulation is presented. Second, studies performed in rats are presented showing medullary blood flow plays a vital role in the pressure-natriuresis relationship and thereby in hypertension. Third, it is shown that chronic reduction of medullary blood flow results in hypertension and that enhancement of medullary blood flow reduces hypertension hereditary models of both salt-sensitive rats and salt-resistant forms of hypertension. The key role that medullary nitric oxide production plays in protecting this region from ischemic injury associated with circulating vasoconstrictor agents and reactive oxygen species is presented. The studies cited are largely the work of my students, research fellows, and colleagues with whom I have performed these studies dating from the late 1980s to more recent years. [ABSTRACT FROM AUTHOR]

Ocean warming is one of the most important factors in shaping the spatial distribution and genetic biodiversity of marine organisms worldwide. The northwest Pacific has been broadly illustrated as an essential seaweed diversity hotspot. However, few studies have yet investigated in this region on whether and how past and ongoing climate warming impacted the distribution and genetic pools of coastal seaweeds. Here, we chose the invasive species Gracilaria vermiculophylla as a model, and identified multiple genetic lineages in the native range through genome-scale microsatellite genotyping. Subsequently, by reconstructing decadal trends of sea surface temperature (SST) change between 1978 and 2018, we found that SST in northern Japan and the East China Sea indeed increased broadly by 0.25-0.4°C/decade. The projections of species distribution models (SDMs) under different future climate change scenarios (RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5) indicated that a unique genetic pool of G. vermiculophylla at its current southern range limit (i.e. the South China Sea) is at high risk of disappearance, and that the populations at its current northern range limit (i.e. in Hokkaido region) will undergo poleward expansions, particularly by the year 2100. Such responses, along with this species’ limited dispersal potential, may considerably alter the contemporary distribution and genetic composition of G. vermiculophylla in the northwest Pacific, and ultimately threaten ecological services provided by this habitat-forming species and other associated functional roles.

The Tokyo 2020 Olympic and Paralympic Games (Games) were held during the height of the coronavirus disease 2019 (COVID-19) pandemic. To detect people infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) early enough to contain the spread and to facilitate the timely arrival of athletes at their game venues, all participating athletes staying in the Olympic Village (up to 14,000) were screened daily for the infection. Toward this aim, a two-step strategy was adopted comprising screening of self-collected saliva samples using a chemiluminescence enzyme immunoassay, followed by confirmatory testing using polymerase chain reaction. The testing system was integrated with an information management system covering all steps. To ensure the accuracy of the test results, rigorous quality assurance measures and monitoring of performance/specimen quality were implemented. A chronological chart analysis was implemented to monitor the holistic process and to give feedback to improve the sampling. Nearly all test results for 418,506 saliva samples were reported within 12 hours of sample collection, achieving the target mean turnaround time of 150 minutes for confirmatory testing. As a result, athlete activity and performance for the Games were ensured. The chronological chart confirmed that no athletes were withdrawn due to a false-positive result, and no infection clusters were identified among the athletes in the Olympic Village. In conclusion, continuous quality improvement as part of the two-step strategy for mass screening for COVID-19 contributed to the success of the Games during the pandemic. The quality practice, systems, and workflows described here may offer a model for future mass-gathering sporting events during similar major infectious disease epidemics. [ABSTRACT FROM AUTHOR]

We have previously observed that prolonged administration of rapamycin, an inhibitor targeting the mammalian target of rapamycin complex (mTORC)1, partially reduced hypertension and alleviated kidney inflammation in Dahl salt-sensitive (SS) rats. In contrast, treatment with PP242, an inhibitor affecting both mTORC1/mTORC2, not only completely prevented hypertension but also provided substantial protection against kidney injury. Notably, PP242 exhibited potent natriuretic effects that were not evident with rapamycin. The primary objective of this study was to pinpoint the specific tubular sites responsible for the natriuretic effect of PP242 in SS rats subjected to either 0.4% NaCl (normal salt) or 4.0% NaCl (high salt) diet. Acute effects of PP242 on natriuretic, diuretic, and kaliuretic responses were determined in unanesthetized SS rats utilizing benzamil, furosemide, or hydrochlorothiazide [inhibitors of epithelial Na+ channel (ENaC), Na-K-2Cl cotransporter (NKCC2), or Na-Cl cotransporter (NCC), respectively] either administered alone or in combination. The findings indicate that the natriuretic effects of PP242 in SS rats stem predominantly from the inhibition of NCC and a reduction of ENaC open probability. Molecular analysis revealed that mTORC2 regulates NCC activity through protein phosphorylation and ENaC activity through proteolytic cleavage in vivo. Evidence also indicated that PP242 also prevents the loss of K+ associated with the inhibition of NCC. These findings suggest that PP242 may represent an improved therapeutic approach for antihypertensive intervention, potentially controlling blood pressure and mitigating kidney injury in salt-sensitive human subjects. NEW & NOTEWORTHY: This study explored mechanisms underlying the natriuretic effects of mammalian target of rapamycin protein complex 2 inhibition using PP242 and revealed both epithelial Na+ channel and Na-Cl cotransporter in the distal tubular segments were potentially inhibited. These observations, with prior lab evidence, indicate that PP242 prevents hypertension via its potent inhibitory effects on these specific sodium transporters and by reducing renal immune responses. This dual action, coupled with potassium sparing effects, suggests an improved approach for managing hypertension and associated kidney damage. [ABSTRACT FROM AUTHOR]

The repeated transgression and regression of coastlines mediated by the late Quaternary glacial–interglacial cycles make the northwest Pacific a hot spot to study marine speciation and population diversity. The red alga Agarophyton vermiculophyllum is an ecologically important species native to the northwest Pacific, capturing considerable research interest due to its wide-range invasiveness in Europe and North America. However, the knowledge of phylogeographic structure and intraspecific genetic diversity across the entire native range was still scarce. Here, we used 1,214-bp of mitochondrial cytochrome c oxidase subunit 1 (cox1) to explore phylogeographic patterns, lineage structure, and population genetic differentiation of 48 A. vermiculophyllum populations in the northwest Pacific. Our DNA data revealed overall high haplotype diversity and low nucleotide diversity and five phylogeographically structured genetic lineages that diverged significantly from each other. S-DIVA analysis showed the ancestors of A. vermiculophyllum originating from multiple areas encompassing the Japan–Pacific coast, East and South China Seas. This combined evidence indicates that A. vermiculophyllum might have survived in multiple scattered glacial refugia during the late Quaternary climate oscillations in the northwest Pacific. Such knowledge may help to better understand how palaeoclimate interacted with contemporary environments to contribute to intraspecific genetic variation and provide a new perspective for conserving natural resource of A. vermiculophyllum in the northwest Pacific.

In this study, novel methods were developed, which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague–Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to 4.0% NaCl diet. In addition, targeted mRNA expression analysis of cortical segments was performed. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. A novel finding was the increased expression of glycolysis-related genes in Cx and isolated proximal tubular segments in response to an HS diet, consistent with increased release of pyruvate and lactate from the kidney to the renal venous blood. Data suggests that aerobic glycolysis (eg, Warburg effect) may contribute to energy production under these circumstances. The study provides evidence that kidney metabolism responds to an HS diet enabling enhanced energy production while protecting from oxidative stress and injury. Metabolomic and transcriptomic analysis of kidneys of Sprague-Dawley rats fed a high salt diet. Graphical Abstract [ABSTRACT FROM AUTHOR]