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BackgroundThe heart develops under reduced and varying oxygen concentrations, yet there is little understanding of oxygen metabolism in the normal and mal‐development of the heart. Here we used a novel reagent, the ODD‐Luc hypoxia reporter mouse (oxygen degradation domain, ODD) of Hif‐1α fused to Luciferase (Luc), to assay the activity of the oxygen sensor, prolyl hydroxylase, and oxygen reserve, in the developing heart. We tested the role of hypoxia‐dependent responses in heart development by targeted inactivation of Hif‐1α.Methods and ResultsODD‐Luciferase activity was 14‐fold higher in mouse embryonic day 10.5 (E10.5) versus adult heart and liver tissue lysates. ODD‐Luc activity decreased in 2 stages, the first corresponding with the formation of a functional cardiovascular system for oxygen delivery at E15.5, and the second after birth consistent with complete oxygenation of the blood and tissues. Reduction of maternal inspired oxygen to 8% for 4 hours caused minimal induction of luciferase activity in the maternal tissues but robust induction in the embryonic tissues in proportion to the basal activity, indicating a lack of oxygen reserve, and corresponding induction of a hypoxia‐dependent gene program. Bioluminescent imaging of intact embryos demonstrated highest activity in the outflow portion of the E13.5 heart. Hif‐1α inactivation or prolonged hypoxia caused outflow and septation defects only when targeted to this specific developmental window.ConclusionsLow oxygen concentrations and lack of oxygen reserve during a critical phase of heart organogenesis may provide a basis for vulnerability to the development of common septation and conotruncal heart defects.

In this study, we used miTAG approach to analyze the distributional pattern and fine‐scale genetic diversity of the ammonia oxidizing archaea (AOA) lineages in the global oceans with the metagenomics data sets of the Tara Oceans global expedition (2009–2013). Using the ammonium monooxygenase alpha subunit gene as a biomarker, the AOA communities in the global oceans were recovered with highly diverse operational taxonomic units that affiliated to previously defined clades, including water column A (WCA), water column B (WCB), and SCM1‐like clades. In general, the AOA communities were obviously segregated with depth (except the upwelling regions), and the communities in the euphotic zones were more heterogeneous than in the mesopelagic zones (MPZs). The WCA distributed more evenly and widely in the euphotic zone and MPZs, while WCB and SCM1‐like clade mainly distributed in MPZ and high‐latitude waters, respectively. At fine‐scale genetic diversity, SCM1‐like and 2 WCA subclades showed distinctive niche separations of distributional pattern. We further divided the AOA subclades into ecological significant taxonomic units (ESTUs), which were delineated from the distribution pattern of their corresponding subclades. For example, ESTUs of WCA have different correlations with depth, nitrate to silicate ratio, and salinity; SCM1‐like A was negatively correlated with irradiation, whereas other SCM1‐like ESTUs preferred low‐temperature and high‐nutrient conditions. Our result showed that the previously defined AOA clades and ecotypes consist of highly diverse sublineages, whose diversity might be overlooked in the past. The distribution patterns of different ESTUs imply their ecophysiological characteristics and potential roles in biogeochemical cycling.

BackgroundOur previous study found that lower lymphocyte-to-monocyte ratio (LMR) is an independent risk factor of clinical outcome of acute ischemic stroke (AIS). However, whether lower LMR is independently associated with adverse prognosis of AIS treated with thrombolysis has not been determined. In this study, we explored the relationship between LMR and prognosis of AIS treated with thrombolysis.Material/MethodsWe retrospectively enrolled 108 patients treated with thrombolysis. LMR was calculated according to lymphocyte count and monocyte count on admission. Patients were classified into 3 groups according to LMR values on admission (group 1 LMR >4.34, group 2 LMR 2.79 to 4.34, group 3 LMR <2.79). Neurologic impairment was estimated by use of the National Institute of Health Stroke Scale. Clinical prognosis at 3 months was assessed by modified Rankin Scale. The relationship between LMR and neurologic impairment was analyzed by Spearman rank correlation. Receiver operating characteristic curve (ROC) was used to evaluate the ability of LMR to predict outcome.ResultsPatients in group 3 had lower lymphocyte counts and LMR values and higher monocyte counts (P<0.001). LMR value was negatively correlated with the degree of neurologic impairment (r=−0.372, P<0.001). The ROC suggested a moderate sensitivity (71.6%) and specificity (80.5%) of LMR for predicting prognosis with an optimal cut-off point at 3.48. Higher LMR value was an independent protective factor against adverse prognosis (odds ratio 0.683, 95% confidence interval 0.490−0.952, P=0.024).ConclusionsA lower LMR value is an independent predictor of poor prognosis of AIS treated with thrombolytic therapy.

We studied picoplankton community structures in the subarctic Pacific Ocean and the Bering Sea during summer 1999 using flow cytometric analysis. The picoplankton community in the studied area was comprised of Synechococcus spp., eukaryotic ultraplankton and heterotrophic bacteria. Prochlorococcus spp. were not detected at any station. Abundances of Synechococcus and eukaryotic ultraplankton were at approximately the same level of 10 3 to 10 4 cells ml -1 within the upper euphotic layer in the subarctic gyres. An abundance of Synechococcus spp. higher than 5 × 10 4 cells ml -1 was found at the surface to 40 m depth in the northern Gulf of Alaska, whereas low Synechococcus spp. abundance (about 500 cells ml -1 ) was found in the upper euphotic layer in the Bering Sea. Abundances of heterotrophic bacteria were about 2 orders of magnitude higher than those of Synechococcus spp. and eukaryotic ultraplankton, with higher abundance generally occurring in the area of high autotrophic biomass. Although Synechococcus spp. and eukaryotic ultraplankton occurred at comparable abundance, the latter contributed significantly more to photosynthetic carbon biomass, except in the northern Gulf of Alaska, where the biomass of Synechococcus spp. and eukaryotic ultraplankton were approximately equal. Cellular red fluorescence for Synechococcus spp. and eukaryotic ultraplankton increased by an average 4-and 2-fold, respectively, from the surface to the bottom of the euphotic layer, with the smallest increase occurring in the Bering Sea. Both the red fluorescence and forward light scatter (FSC, related mainly to cell size) per cell varied more than 2-fold spatially, with the highest value occurring in the Bering Sea. These variations were probably caused by differences in physiological conditions and species compositions. Overall, picophytoplankton was the dominant contributor to total autotrophic biomass in the subarctic North Pacific, but contributed only a small fraction to total autotrophic biomass in the Bering Sea. The Western Gyre (WG) and the Alaskan Gyre (AG) possess both similarities and differences in biogeochemical processes and microbial food-web dynamics. The slightly higher phytoplankton biomass, photosynthetic efficiencies and growth rates in WG than AG suggests less severe iron limitation in the WG.