Do Strong Winds Impact Water Mass, Nutrient, and Phytoplankton Distributions in the Ice‐Free Canada Basin in the Fall?

In general, strong wind events can enhance ocean turbulent mixing, followed by episodic nutrient supply to the euphotic zone and phytoplankton blooms. However, it is unclear whether such responses to strong winds occur in the ice‐free Canada Basin, where the seasonal pycnocline is strong and the nutricline is deep. In the present study, we monitored a fixed‐point observation (FPO) station in the Canada Basin for about 3 weeks in the fall of 2014 to examine the oceanic and biological responses to strong winds. At the FPO site, oceanic microstructure measurements, hydrographic surveys, and water sampling were performed with high temporal resolution, recording internal wave propagation, eddy passage, and water mass changes. Strong winds and internal wave propagation significantly enhanced the mixing above and at the seasonal pycnocline, but their effects were diminished at the nutricline, which was much deeper than the seasonal pycnocline. Therefore, wind‐induced mixing did not increase the upward nutrient supply from the nutricline and did not impact phytoplankton (chlorophyll a) distribution in the surface layer of the FPO site. The temporal evolution of the chlorophyll a concentration was most closely related to water mass changes. We also observed prominent subsurface chlorophyll a maxima with abundant large‐sized phytoplankton that were likely carried by warm‐core eddies to the FPO site. Phytoplankton biomass may have been sustained by the high concentration of ammonium within the eddy and ammonium regeneration at the seasonal pycnocline, where particulate organic matter likely accumulated

The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

BackgroundSevere protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).ProcedureWe studied the onset of disease and the genotype of 22 PCâ deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.ResultsTwentyâ two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19â 52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six lateâ onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset.ConclusionsThe genotype of doubleâ PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137364/1/pbc26404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137364/2/pbc26404.pd

Association of breast feeding with early childhood dental caries: Japanese population-based study

Objectives: We investigated the association between breastfeeding duration during the first half year of life and the risk of early childhood caries from the age of 30 to 66 months in Japan. Design: Observational study of a longitudinal survey. Setting: A secondary data analysis of the Japanese Longitudinal Survey of Babies in the 21st Century. Participants: 43 383 infants at the age of 6 months. Outcome measures Early childhood caries—defined as a child's visit to a dentist for treatment of dental caries during the past 12 months—was ascertained from the caregiver from the age of 30 months in the survey. We estimated the risk of dental caries each year according to duration of breast feeding using logistic regression analyses. We controlled for a set of biological factors (birth weight, sex, parity and maternal age at delivery) and socioeconomic factors (maternal educational attainment and smoking status, marital status at delivery, family income and region of birth and residence). Results: We found that infants who had been breast fed for at least 6 or 7 months, both exclusively and partially, were at elevated risk of dental caries at the age of 30 months compared with those who had been exclusively formula fed. Adjusted ORs were 1.78 (95% CI, (1.45 to 2.17)) for the exclusively breastfed group and 1.39 (1.14 to 1.70) for the partially breastfed group. However, the associations became attenuated through the follow-up period and were no longer statistically significant beyond the age of 42 months for the partially breastfed group and beyond the age of 54 months for the exclusively breastfed group. Conclusions: We found an association between breast feeding for at least 6 or 7 months and elevated risk of dental caries at age 30 months. However, the association became attenuated as children grew older

シンエコー ドップラーホウ ニヨル ソウボウベンリン セッカイカ ニ トモナウ ベンリン キョウサク ノ ジュウショウド ヒョウカ

Recently, mitral annular calcification (MAC) is a common finding with increasing of elderly orrenal failure patients. Mitral stenosis secondary to MAC is not rarely observed. Pressure halftime method by continuous wave Doppler echocardiography is often used to evaluate the severityof the stenotic mitral valve due to MAC. But, the method for calculating correct mitral orifice areais not established. We performed transthoracic Doppler echocardiography and cardiac catheterizationin 15 patients with rheumatic mital stenosis and 10 with mitral stenosis due to MAC, and calculatedthe severity of the mitral stenosis by pressure half time (PHT), continuity equation methods andGorlin formula. Pulsed tissue Doppler imaging methods were used for evaluating left ventricular(LV) early diastolic wall motion velocities. Results were as follows. 1) The mitral orifice areas determinedby PHT method were lower than those by continuity equation methods or Gorlin formulain patients with mitral stenosis due to MAC, and significant correlation was observed in rheumaticmital stenosis between the mitral orifice areas obtained by PHT and continuity equation methods,but not in mitral stenosis due to MAC. 2) The peak early diastolic LV myocardial velocities alonglong and short axes decreased significantly in mitral stenosis due to MAC than those in rheumaticmital stenosis. In conclusion, as mitral orfice area determined from PHT method is strongly influencedby early diastolic LV dysfunction in mitral stenosis due to MAC, continuity equation methodshould be recommended

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development

High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1-activation also occurs in vascular endothelial cells (ECs), including those of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1-Gi axis in HEVs, we generated Lyve1;Spns2Δ/Δ conditional knockout mice for the S1P-transporter Spinster-homologue-2 (SPNS2), as HEVs express LYVE1 during development. In these mice HEVs appeared apoptotic and were severely impaired in function, morphology and size; leading to markedly hypotrophic peripheral LNs. Dendritic cells (DCs) were unable to interact with HEVs, which was also observed in Cdh5CRE-ERT2;S1pr1Δ/Δ mice and wildtype mice treated with S1PR1-antagonists. Wildtype HEVs treated with S1PR1-antagonists in vitro and Lyve1-deficient HEVs show severely reduced release of the DC-chemoattractant CCL21 in vivo. Together, our results reveal that EC-derived S1P warrants HEV-integrity through autocrine control of S1PR1-Gi signaling, and facilitates concomitant HEV-DC interactions.Simmons S., Sasaki N., Umemoto E., et al. High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node. eLife 8, e41239 (2019); https://doi.org/10.7554/eLife.41239