Quantifying the biologically possible range of steady-state soil and surface climates with climate model simulations

The terrestrial biosphere shapes the exchange fluxes of energy and mass at the land surface. The diversity of plant form and functioning can potentially result in a wide variety of possible climatic conditions at the land surface and in the soil, which in turn feed back to more or less suitable conditions for terrestrial productivity. Here, I use sensitivity simulations to vegetation form and functioning with a global climate model to quantify this possible range of steady-states (“PROSS”) of the surface energy-and mass balances. The surface energy-and water balances over land are associated with substantial sensitivity to vegetation parameters, with precipitation varying by more than a factor of 2, and evapotranspiration by a factor of 5. This range in biologically possible climatic conditions is associated with drastically different levels of vegetation productivity. Optimum conditions for maximum productivity are close to the simulated climate of present-day conditions. These results suggest the conclusions that (a) climate does not determine vegetation form and function, but merely constrains it, and (b) the emergent climatic conditions at the land surface seem to be close to optimal for the functioning of the terrestrial biosphere.     

Influence of different vegetation types on saturated hydraulic conductivity in alluvial topsoils

In the Parí? creek catchment (southwestern part of Slovakia), the influence of different vegetation types on selected soil properties in alluvial topsoils was studied. Specifically, the effect on saturated hydraulic conductivity considered as indicator of water transport process and the effect on soil bulk density considered as indicator of soil structure were analysed. Due to the mutual influence of plant roots on soil properties, the root biomass was also estimated and its relationship to the studied soil properties was explored. Reed and tall-sedge wetlands and alluvial wet meadows represented the studied vegetation types. Adjacent arable lands (former grasslands) with corn were included for comparison. In total, 64 samples were used for comparative analysis. A standard methodology for measurement of the saturated hydraulic conductivity, the so-called falling head technique was used on 250 cm³ soil cores. Undisturbed soil samples were taken from the depth of 5 cm. Analysis of variance, mutual comparison of mean values and correlation matrix were used for statistical analyses. Measurements showed significantly higher values of saturated hydraulic conductivity for topsoils in wetlands (6.2 m day^?1 on average) compared to mown grasslands (1.47 m day^?1) and arable land (0.79 m day^?1). The results indicated a specific significance of wetlands in relation to water transport processes in alluvial topsoils.     

Ischemia impairs the association between connexin 43 and M3 subtype of acetylcholine muscarinic receptor (M3-mAChR) in ventricular myocytes.

We used Western blot analysis to examine the expression of connexin 43 and M2/M3 acetylcholine muscarinic receptors (mAChR) and their interaction in ventricular myocytes from control and the ischemic heart. We confirmed that the connexin 43 and M2/ M3-mAChR were expressed in ventricular myocytes. Moreover, we showed that M3-mAChR was expressed in non-glycosylated (72 kDa) and glycosylated forms (115 kDa). Immunostaining showed that connexin 43 is closely associated with M3-mAChR in parts of cell membranes of myocytes. Immunoprecipitation of lysate of cardiac myocytes with M2/M3-mAChR antibody pulled down a 44 kDa protein recognized by connexin 43 antibody. Ischemia increased the expression of M3-mAChR in myocytes. The ischemiainduced increase in the M3-mAChR expression was specific because ischemia did not affect the expression of M1, M2, M4 and M5- mAChR in the heart. On the other hand, ischemia decreased the expression of connexin 43 in myocardium. We also examined the effect of ischemia on the interaction between M2/M3-mAChR and connexin 43. Ischemia suppressed the association of M3-mAChR with connexin 43 but did not affect the association of connexin 43 with M2-mAChR. Administration of choline before ischemia not only partially restored the expression of connexin 43 but also attenuated the ischemia-induced suppression of the association between connexin 43 and M3-mAChR. We conclude that connexin 43 interacts with M2/M3-mAChR and that ischemia specifically impairs the association between M3-mAChR and connexin 43.     

Ordered subset linkage analysis based on admixture proportion identifies new linkage evidence for alcohol dependence in African-Americans

Genetic heterogeneity could reduce the power of linkage analysis to detect risk loci for complex traits such as alcohol dependence (AD). Previously, we performed a genomewide linkage analysis for AD in African-Americans (AAs) (Biol Psychiatry 65:111–115, 2009). The power of that linkage analysis could have been reduced by the presence of genetic heterogeneity owing to differences in admixture among AA families. We hypothesized that by examining a study sample whose genetic ancestry was more homogeneous, we could increase the power to detect linkage. To test this hypothesis, we performed ordered subset linkage analysis in 384 AA families using admixture proportion as a covariate to identify a more homogeneous subset of families and determine whether there is increased evidence for linkage with AD. Statistically significant increases in lod scores in subsets relative to the overall sample were identified on chromosomes 4 (P = 0.0001), 12 (P = 0.021), 15 (P = 0.026) and 22 (P = 0.0069). In a subset of 44 families with African ancestry proportions ranging from 0.858 to 0.996, we observed a genomewide significant linkage at 180 cM on chromosome 4 (lod = 4.24, pointwise P < 0.00001, empirical genomewide P = 0.008). A promising candidate gene located there, GLRA3, which encodes a subunit of the glycine neurotransmitter receptor. Our results demonstrate that admixture proportion can be used as a covariate to reduce genetic heterogeneity and enhance the detection of linkage for AD in an admixed population such as AAs. This approach could be applied to any linkage analysis for complex traits conducted in an admixed population.     

Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells

Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer.     

Characterization of Basal and Morphine-Induced Uridine Release in the Striatum: An In Vivo Microdialysis Study in Mice

Uridine, a pyrimidine nucleoside, has been proposed to be a potential signaling molecule in the central nervous system. The understanding of uridine release in the brain is therefore of fundamental importance. The present study was performed to determine the characteristics of basal and morphine-induced uridine release in the striatum of freely moving mice by using the microdialysis technique. To ascertain whether extracellular uridine was derived from neuronal release, the following criteria were applied: sensitivity to (a) K⁺ depolarization, (b) Na⁺ channel blockade and (c) removal of extracellular Ca²⁺. Uridine levels were not greatly affected by infusion of tetrodotoxin (TTX) and were unaffected by either Ca²⁺-free medium or in the presence of EGTA (a calcium chelator), suggesting that basal extracellular uridine levels were maintained mainly by non-vesicular release mechanisms. In addition, both systemic and local application of morphine increased striatal uridine release. The morphine-induced release was reversed by naloxone pretreatment, but was unaffected by TTX or EGTA infusion. Moreover, co-administration of morphine and nitrobenzylthioinosine (NBTI, an inhibitor of nucleotide transporter) produced increases of uridine levels similar to that produced by NBTI or morphine alone, suggesting a nucleotide transporter mechanism involved. Taken together, these findings suggest that morphine produces a μ-opioid receptor-mediated uridine release via nucleoside transporters in a TTX- and calcium-independent manner.     

Loss of microRNA-132 predicts poor prognosis in patients with primary osteosarcoma

??₂-glycoprotein I (??₂-GPI) is a plasma glycoprotein with diverse functions, but the impact and molecular effects of ??₂-GPI on vascular biology are as yet unclear. Based on the limited information available on the contribution of ??₂-GPI to endothelial cells, we investigated the effect of ??₂-GPI on cell growth and migration in human aortic endothelial cells (HAECs). The regulation of ??₂-GPI as part of intracellular signaling in HAECs was also examined. Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that may regulate endothelial functions. We found that ??₂-GPI dose-dependently inhibited VEGF-induced endothelial cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-dipenyl tetrazolium bromide assay and cell counts. Using wound healing and Boyden chamber assays, ??₂-GPI remarkably reduced VEGF-increased cell migration at the physiological concentration. Furthermore, ??₂-GPI suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2), extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt. These results suggest that ??₂-GPI plays an essential role in the down-regulation of VEGF-induced endothelial responses and may be a useful component for anti-angiogenic therapy.     

Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion

MicroRNAs (miRNA) precursor (pre-miRNA) molecules can be processed to release a miRNA/miRNA* duplex. In the canonical model of miRNA biogenesis, one strand of the duplex is thought to be the biologically active miRNA, whereas the other strand is thought to be inactive and degraded as a carrier or passenger strand called miRNA* (miRNA star). However, recent studies have revealed that miRNA* strands frequently play roles in the regulatory networks of miRNA target molecules. Our recent study indicated that miR-17 transgenic mice could abundantly express both the mature miR-17-5p and the passenger strand miR-17-3p. Here, we showed that miR-17 enhanced prostate tumor growth and invasion by increasing tumor cell proliferation, colony formation, cell survival and invasion. miRNA target analysis showed that both miR-17-5p and miR-17-3p repressed TIMP metallopeptidase inhibitor 3 (TIMP3) expression. Silencing with small interfering RNA against TIMP3 promoted cell survival and invasion. Ectopic expression of TIMP3 decreased cell invasion and cell survival. Our results demonstrated that mature miRNA can function coordinately with its passenger strand, enhancing the repressive ability of a miRNA by binding the same target. Within an intricate regulatory network, this may be among the mechanisms by which miRNA can augment their regulatory capacity.