NO is a major regulator of cardiovascular physiology that reduces vascular and cardiac contractility. Accumulating evidence indicates that endogenous inhibitors may regulate NOS. The NOS inhibitors ...asymmetric dimethylarginine (ADMA) and N-monomethylarginine are metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). This study was designed to determine if increased expression of DDAH could reduce tissue and plasma levels of the NOS inhibitors and thereby increase NO synthesis.
We used gene transfer and transgenic approaches to overexpress human DDAH I in vitro and in vivo. The overexpression of DDAH in cultured endothelial cells in vitro induced a 2-fold increase in NOS activity and NO production. In the hDDAH-1 transgenic mice, we observed approximately 2-fold increases in tissue NOS activity and urinary nitrogen oxides, associated with a 2-fold reduction in plasma ADMA. The systolic blood pressure of transgenic mice was 13 mm Hg lower than that of wild-type controls (P<0.05). The systemic vascular resistance and cardiac contractility were decreased in response to the increase in NO production.
DDAH I overexpression increases NOS activity in vitro and in vivo. The hDDAH-1 transgenic animal exhibits a reduced systolic blood pressure, systemic vascular resistance, and cardiac stroke volume. This study provides compelling evidence that the elaboration and metabolism of endogenous ADMA plays an important role in regulation of NOS activity.
Marginal zone (MZ) B cells mount rapid T-cell-independent (T-I) immune responses against microbial components such as LPS. While Toll-like receptor 4 (TLR4) is essential for LPS responses, MZ B cells ...uniquely express high levels of another LPS sensor Radioprotective 105 (RP105). However, little is known about how RP105 is used by MZ B cells. In this study, we investigated TLR4- or RP105-dependent MZ B cell responses by utilizing agonistic monoclonal antibodies (mAbs) to each receptor. Cross-linking TLR4 and RP105 at the same time with the mAbs induced robust IgM-secreting plasma cell generation as lipid A moiety of LPS. In contrast, stimulation with either mAb alone did not elicit such responses. RP105-deficient MZ B cells failed to produce IgM-secreting plasma cells in response to lipid A. TLR4 or lipid A stimulation of MZ B cells up-regulated their B lymphocyte-induced maturation protein 1 (Blimp-1) and X-box-binding protein 1 (Xbp-1) mRNA expression. RP105 stimulation alone did not give these responses and in fact decreased TLR4-mediated their expression. Compared with wild-type (WT) MZ B cells, RP105-deficient MZ B cells exhibited increased levels of Blimp-1 and Xbp-1 mRNA expression in response to lipid A. Lipid A or TLR4 plus RP105 stimulation induced massive proliferation and expression of Bcl-xL and c-Myc in WT but not RP105-deficient MZ B cells. These responses contributed to TLR4-mediated anti-apoptotic responses in MZ B cells. Thus, RP105 contributes in a unique way to the TLR4-dependent survival, proliferation and plasma cell generation of MZ B cells.
To examine the influence of both crop cultivation and surface air temperatures (SATs) on annual global isoprene and monoterpene emissions, which can lead to the formation of secondary organic ...aerosols (SOAs), we simulated, on a monthly basis, the annual emissions of volatile organic compounds (VOCs) during the period 1854–2000. The model estimates were based on historical climate data such as SATs, and downward solar radiation (DSR) reproduced with an atmospheric-ocean circulation model, as well as a time series of the global distribution of cropland (to test the hypothesis that conversion of forests into croplands lowers emissions). The simulations demonstrated that global SAT, DSR, the combination of SAT and DSR, and the expansion of cropland all affected emissions. The effect of cropland expansion (i.e., forest conversion) on annual emissions during this period was larger for isoprene (~7% reduction on a global scale) than for monoterpenes (~2% reduction), mainly because of the reduction in broadleaf evergreen forests (BEFs) in Southeast Asia, which have the highest and most constant emissions of isoprene and where both temperature and radiation are high all year round. The reduction in the Amazon region and in parts of Africa, which are other primary sources of annual global isoprene emissions, but where the conversion of BEF to cropland has been much smaller than in Southeast Asia, was less remarkable, probably because the broadleaf deciduous forests and C4 grasslands in these areas have lower and seasonal emissions; hence, their conversion has less effect. On the other hand, the difference in the emission factors (ε) between cropland and the other vegetation types was much lower for monoterpenes than for isoprene, although the ε for cropland was generally the lowest for both compounds. Thus, the expansion of cropland also contributed to the reduction in monoterpene emissions to some degree, but had less effect. A ~5% increase in emissions due to rising SAT was more than offset by the decrease in isoprene emissions and a concurrent ~2% reduction caused by a decrease in DSR. Overall, annual global isoprene emissions in 2000 were lower than in 1854 by 13 TgC yr−1, whereas annual global monoterpene emissions were higher by 2.3 TgC yr−1.
Direct site-specific biotinylation of RNA molecules was achieved by specific transcription mediated by unnatural base pairs. Unnatural base pairs between 2-amino-6-(2-thienyl)purine (denoted by s) ...and 2-oxo(1H)pyridine (denoted by y), or 2-amino-6-(2-thiazolyl)purine (denoted as v) and y specifically function in T7 transcription. Using these unnatural base pairs, the substrate of biotinylated-y (Bio-yTP) was selectively incorporated into RNA, opposite s or v in the DNA templates, by T7 RNA polymerase. This method was applied to the immobilization of an RNA aptamer on sensor chips, and the aptamer accurately recognized its target protein. This direct site-specific biotinylation will provide a tool for RNA-based biotechnologies.
Historical wintertime sea surface temperature (SST) data show that a sandwich pattern dominates on the decadal timescales in the North Atlantic, at least after the 1970s. The authors investigated how ...such decadal SST anomalies can survive against local thermal feedback, which acts to dampen them rapidly. At the surface, winter SST anomalies have a negligible projection with the subsequent summer anomalies while they show a significant projection with the SST anomalies in the next winter. On the other hand, observed summer temperature anomalies below the mixed layer tend to have the same sign as the previous winter SST anomalies, although the magnitude of the former is roughly one-third of the latter. This suggests that a reemergence mechanism of SST anomalies associated with the seasonal cycle of the mixed layer depth (MLD), which has been verified by Alexander and Deser, helps maintain the decadal SST anomalies. In order to examine this scenario, a mixed layer model driven by daily atmospheric data generated by a T42 atmospheric general circulation model was used. The mixed layer model well reproduces the climatology of both SST and MLD in the North Atlantic. An experiment in which a thermal forcing having the observed decadal pattern is added only for the initial winter shows that the SST anomalies disappear until July but reappear in the subsequent winters. This result supports the inference based on the observational evidence, and is explained as follows: (i) SST anomalies are partly detrained to deeper levels in spring when the mixed layer shoals rapidly, (ii) temperature anomalies beneath the shallow mixed layer are preserved during summer, (iii) they are entrained into the surface in the succeeding fall and winter when the mixed layer is again deepened. The recurrence of SST anomalies was found in two centers of the decadal anomaly pattern (30°–45°N, 80°–50°W and 45°–60°N, 50°–20°W), but not in another center in the subtropics (10°–25°N, 40°–10°W) where the MLD reveals only a small seasonality. The magnitude of recurrent SST anomalies is affected by two factors: MLD difference between winter and summer and the persistence of SST anomalies from winter to spring as they determine the amount and the magnitude of detrained temperature anomalies into the mixed layer, respectively.
The above results indicate that the effective damping time for the winter SST anomalies is much longer than the local damping time of several months.
The sixth version of the Model for Interdisciplinary Research on Climate
(MIROC), called MIROC6, was cooperatively developed by a Japanese modeling
community. In the present paper, simulated mean ...climate, internal
climate variability, and climate sensitivity in MIROC6 are evaluated and
briefly summarized in comparison with the previous version of our climate
model (MIROC5) and observations. The results show that the overall
reproducibility of mean climate and internal climate variability in MIROC6
is better than that in MIROC5. The tropical climate systems (e.g.,
summertime precipitation in the western Pacific and the eastward-propagating
Madden–Julian oscillation) and the midlatitude atmospheric circulation
(e.g., the westerlies, the polar night jet, and troposphere–stratosphere
interactions) are significantly improved in MIROC6. These improvements can
be attributed to the newly implemented parameterization for shallow
convective processes and to the inclusion of the stratosphere. While there
are significant differences in climates and variabilities between the two
models, the effective climate sensitivity of 2.6 K remains the same because
the differences in radiative forcing and climate feedback tend to offset
each other. With an aim towards contributing to the sixth phase of the
Coupled Model Intercomparison Project, designated simulations tackling a
wide range of climate science issues, as well as seasonal to decadal climate
predictions and future climate projections, are currently ongoing using
MIROC6.
One of the earliest events in the process of leaf senescence is dismantling of chloroplasts. Mesophyll cell chloroplasts from rosette leaves were studied in Arabidopsis thaliana undergoing natural ...senescence. The number of chloroplasts decreased by only 17% in fully yellow leaves, and chloroplasts were found to undergo progressive photosynthetic and ultrastructural changes as senescence proceeded. In ultrastructural studies, an intact tonoplast could not be visualized, thus, a 35S-GFP::delta-TIP line with a GFP-labeled tonoplast was used to demonstrate that chloroplasts remain outside of the tonoplast even at late stages of senescence. Chloroplast DNA was measured by real-time PCR at four different chloroplast loci, and a fourfold decrease in chloroplast DNA per chloroplast was noted in yellow senescent leaves when compared to green leaves from plants of the same age. Although chloroplast DNA did decrease, the chloroplast/nuclear gene copy ratio was still 31:1 in yellow leaves. Interestingly, mRNA levels for the four loci differed: psbA and ndhB mRNAs remained abundant late into senescence, while rpoC1 and rbcL mRNAs decreased in parallel to chloroplast DNA. Together, these data demonstrate that, during senescence, chloroplasts remain outside of the vacuole as distinct organelles while the thylakoid membranes are dismantled internally. As thylakoids were dismantled, Rubisco large subunit, Lhcb1, and chloroplast DNA levels declined, but variable levels of mRNA persisted.
Changes in east Asian circulation pattern are investigated by the most recent versions of coupled climate models, one a high resolution version of the CCSR/NIES/FRCGC model and the other an ensemble ...of 17 state‐of‐the‐art models made available by the international modeling community. These recent model results appear to give more credence to the following aspects: weakened winter monsoon associated with the shallower and northeastward shifted planetary wave trough over the east coast of the Eurasian Continent and increased activity of east Asian monsoonal rain band in summer associated with the strengthening of anticyclonic cells to its south and north.
Two versions of a coupled atmosphere‐ocean general circulation model (GCM) with different climate sensitivities are tested on global cooling following the Pinatubo volcanic eruption to investigate ...the validity of high climate sensitivities. The higher‐sensitivity version, with climate sensitivity of 6.3 K for doubled CO2 forcing, overestimates cooling due to the volcanic eruption, whereas the lower‐sensitivity version (4.0 K) produces results consistent with observations. A simple scheme for climate feedback analysis is devised and it is found that the difference between the two versions is attributed to cloud‐albedo feedback. This validation method is expected to provide additional constraints on climate sensitivity and possibly lead to reduced uncertainties in climate prediction.
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