Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility.

Localization of the N-methyl-D-aspartate type glutamate receptor (NMDAR) to dendritic spines is essential for excitatory synaptic transmission and plasticity. Rather than remaining trapped at synaptic sites, NMDA receptors undergo constant cycling into and out of the postsynaptic density. Receptor movement is constrained by protein-protein interactions with both the intracellular and extracellular domains of the NMDAR. The role of extracellular interactions on the mobility of the NMDAR is poorly understood. Here we demonstrate that the positive surface charge of the hinge region of the N-terminal domain in the GluN1 subunit of the NMDAR is required to maintain NMDARs at dendritic spine synapses and mediates the direct extracellular interaction with a negatively charged phospho-tyrosine on the receptor tyrosine kinase EphB2. Loss of the EphB-NMDAR interaction by either mutating GluN1 or knocking down endogenous EphB2 increases NMDAR mobility. These findings begin to define a mechanism for extracellular interactions mediated by charged domains

Study on Evolvement Complexity in an Artificial Stock Market

An artificial stock market is established based on multi-agent . Each agent has a limit memory of the history of stock price, and will choose an action according to his memory and trading strategy. The trading strategy of each agent evolves ceaselessly as a result of self-teaching mechanism. Simulation results exhibit that large events are frequent in the fluctuation of the stock price generated by the present model when compared with a normal process, and the price returns distribution is L\'{e}vy distribution in the central part followed by an approximately exponential truncation. In addition, by defining a variable to gauge the "evolvement complexity" of this system, we have found a phase cross-over from simple-phase to complex-phase along with the increase of the number of individuals, which may be a ubiquitous phenomenon in multifarious real-life systems.Comment: 4 pages and 4 figure

Combined associations of 25-hydroxivitamin D and parathyroid hormone with diabetes risk and associated comorbidities among U.S. white and black women

Background/objectives: There is evidence of black–white differences in vitamin D status and cardiometabolic health. This study aimed to further evaluate the joint associations of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) with risks of diabetes and related cardiometabolic comorbidities among white and black women. Subjects/methods: We cross-sectionally and prospectively analyzed data from 1850 black and 3000 white postmenopausal women without cardiovascular disease or dialysis at baseline from the Women’s Health Initiative—Observational Study. Weighted Cox proportional hazards analyses and weighted logistic regression models were used to examine the joint associations of 25(OH)D and PTH with incident diabetes and prevalence of other diabetes-related cardiometabolic comorbidities (including CKD, hypertension, or obesity). Results: We identified 3322 cases of obesity (n = 1629), hypertension (n = 2759), or CKD (n = 318) at baseline and 453 incident cases of diabetes during 11 years of follow-up. Cross-sectionally, lower 25(OH)D and higher PTH were independently associated with higher prevalence of hypertension [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.72–0.87 and OR = 1.55; 95% CI: 1.39–1.73] among white women only. When stratified by diabetes status, compared to women with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L (65 pg/mL), women who did not have diabetes with vitamin D deficiency (6.89 pmol/L) had higher prevalence of CKD, hypertension, or obesity (OR = 4.23; 95% CI: 2.90–6.18) than women who had diabetes (OR = 1.89; 95% CI: 0.96–3.71). Prospectively, lower 25(OH)D was associated with lower diabetes incidence [hazard ratio (HR) = 0.73; 95% CI: 0.62–0.86] in white women. Jointly, compared to the group with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L, white women with 25(OH)D deficiency (<50 nmol/L) had elevated risk for diabetes, regardless of PTH levels. Conclusions: Low 25(OH)D and high PTH were jointly associated with increased risk of diabetes among white women only. Their joint associations with high prevalence of CKD, hypertension, and obesity were more pronounced among women without diabetes

Small anisotropy of the lower critical field and s±s_\pm-wave two-gap feature in single crystal LiFeAs

The in- and out-of-plane lower critical fields and magnetic penetration depths for LiFeAs were examined. The anisotropy ratio $\gamma_{H_{c1}}(0)$ is smaller than the expected theoretical value, and increased slightly with increasing temperature from 0.6$T_c$ to $T_c$. This small degree of anisotropy was numerically confirmed by considering electron correlation effect. The temperature dependence of the penetration depths followed a power law($\sim$$T^n$) below 0.3$T_c$, with $n$$>$3.5 for both $\lambda_{ab}$ and $\lambda_c$. Based on theoretical studies of iron-based superconductors, these results suggest that the superconductivity of LiFeAs can be represented by an extended $s_\pm$-wave due to weak impurity scattering effect. And the magnitudes of the two gaps were also evaluted by fitting the superfluid density for both the in- and out-of-plane to the two-gap model. The estimated values for the two gaps are consistent with the results of angle resolved photoemission spectroscopy and specific heat experiments.Comment: 10 pages, 5 figure

Nanoscale probing of electron-regulated structural transitions in silk proteins by near-field IR imaging and nano-spectroscopy

Silk protein fibres produced by silkworms and spiders are renowned for their unparalleled mechanical strength and extensibility arising from their high-β-sheet crystal contents as natural materials. Investigation of β-sheet-oriented conformational transitions in silk proteins at the nanoscale remains a challenge using conventional imaging techniques given their limitations in chemical sensitivity or limited spatial resolution. Here, we report on electron-regulated nanoscale polymorphic transitions in silk proteins revealed by near-field infrared imaging and nano-spectroscopy at resolutions approaching the molecular level. The ability to locally probe nanoscale protein structural transitions combined with nanometre-precision electron-beam lithography offers us the capability to finely control the structure of silk proteins in two and three dimensions. Our work paves the way for unlocking essential nanoscopic protein structures and critical conditions for electron-induced conformational transitions, offering new rules to design protein-based nanoarchitectures.National Science Foundation (U.S.) (1563422)National Science Foundation (U.S.) (1562915

Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

<p>Abstract</p> <p>Background</p> <p>Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats.</p> <p>Results</p> <p>Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a <it>P</it>-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail.</p> <p>Conclusion</p> <p>The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks.</p

Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation.</p> <p>Methods</p> <p>To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs).</p> <p>Results</p> <p>Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 <it>vs. </it>11.02 ± 8.03, <it>p </it>= 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 <it>vs</it>. 1.22 ± 0.66, <it>p </it>< 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls.</p> <p>Conclusion</p> <p>Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.</p