Molecular Basis of PIP2-dependent Conformational Switching of Phosphorylated CD44 in binding FERM

Association of the cellular adhesive protein CD44 and the N-terminal (FERM) domain of cytoskeleton adaptors is critical for cell proliferation, migration and signaling. Phosphorylation of the cytoplasmic domain (CTD) of CD44 acts as an important regulator of the protein association, but the structural transformation and dynamics mechanism remain enigmatic. In this study, extensive coarse-grained simulations were employed to explore the molecular details in the formation of CD44-FERM complex under S291 and S325 phosphorylation, a modification path known to exert reciprocal effects on the protein association. We find that phosphorylation of S291 inhibits complexation by causing the CTD of CD44 to adopt a more closed structure. In contrast, S325 phosphorylation liberates the CD44-CTD from the membrane surface and promotes the linkage with FERM. The phosphorylation-driven transformation is found to occur in a PIP2-dependent manner, with PIP2 effecting the relative stability of the closed and open conformation, and a replacement of PIP2 by POPS greatly abrogates this effect. The revealed interdependent regulation mechanism by phosphorylation and PIP2 in the association of CD44 and FERM further strengthens our understanding of the molecular basis of cellular signaling and migration.</p

Spatial and temporal hydrochemical variations of the spring-fed travertine-depositing stream in the Huanglong Ravine, Sichuan, SW China

Automatic hydrochemical logging and in situ titration com­bined withlaboratory analysis were used to understand the spatial and temporal hydrochemical variations of the spring-fed, travertine-depositing stream in celebrated Huanglong Ravine, Sichuan, SW China. This is essential for protection of the Huanglong World Natural Heritage travertine land­scape. It was found that the deposition of travertine was due to very strong CO2 degassing from the water, leading to de­crease in pCO2 and specific conductivity (SpC), and increase in pH and SIc downstream from the Spring. However, regular downstream hydrochemical evolution was interrupted by di­lution withsnow-melt water and by renewed CO2 from some downstream springs. The chemistry of Huanglong Spring itself was stable at a diurnal scale thoughit was altered by the great Wenchuan earthquake of May 12 2008. However, in spring-fed pools downstream, pCO2 and SpC were lower, and pH and SIc were higher in daytime than at night, whichindicates that the deposition of travertine was faster during the daylight hours. This was due to the combined effects of higher water tempera­tures and higher aquatic algae photosynthesis. In addition, it was found that the phosphate concentration in the stream in­creased remarkably downstream in the tourist midseason, in­dicating water pollution by tourism activities. The increase of phosphate (an inhibitor of calcite precipitation) may be one of the reasons for the decrease in travertine deposition rates and accelerated propagation of discoloration by diatoms during the past decades, whichneeds to be given more comprehensive study and tackled in future for the protection of these world famous travertine deposits

Identification of the Conformational transition pathway in PIP2 Opening Kir Channels

The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2

The Intelligent Transportation System Using the Infrared Sensors Based on the ZigBee Protocol and Eclipse

There are more and more cars. The traffic jam cost people a lot of time on the road. This system got the number of the cars in waiting on every crossroad by the infrared sensors in the CC2530. Based on the Zigbee protocol, the routers embedded in the infrared sensors sent the information of cars in waiting to the coordinator wirelessly. Then the coordinator sent the information to the website which is developed on the Eclipse platform through the serial port. People can check the designated crossroad whether there is the traffic jam by smart telephone or the web browser. This system can release the newest information. It can be widely applied in the transportation system

Identification of the Conformational transition pathway in PIP2 Opening Kir Channels

The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2 regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2

Lead and copper-induced hormetic effect and toxicity mechanisms in lettuce (Lactuca sativa L.) grown in a contaminated soil

Lead (Pb) and copper (Cu) contamination seriously threatens agricultural production and food safety. This study aims to investigate Pb and Cu induced hormetic effect and toxicity mechanisms in lettuce (Lactuca sativa L.) and establish reliable empirical models of potentially toxic elements (PTEs) transfer in the soil–plant system. The content and distribution of Pb and Cu at subcellular levels in lettuce plants were examined using inductively coupled plasma-mass spectrometry, differential centrifugation and micro-X-ray fluorescence spectroscopy. The PTE-loaded capacity of Pb that ensures food safety was lower than that of Cu in the studied soil, but the PTE-loaded capacity of Pb that limits yield was higher than that of Cu. Lead in lettuce roots mainly accumulated in the cell wall (41%), while Cu mainly accumulated in the vacuoles (46%). The Pb and Cu were primarily distributed in the radicle of lettuce seeds under severe PTE stress, resulting in no seed development. Iron plaque formed on the root surface of lettuce seedlings and sequestered Pb and Cu via chelation. At the same concentration, lettuce was less tolerant to Cu in contaminated soil than Pb due to the higher activity of Cu ions in the soil. Lead was more phytotoxic to lettuce than Cu, however, since the radicle emerged from the seed under severe Cu levels, while it did not protrude under severe Pb levels. The potentially damaging effect of Pb in the visually healthy lettuce appeared to be higher than that of Cu under the same soil contamination level

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Balancing the Lifetime and Storage Overhead on Error Correction for Phase Change Memory.

As DRAM is facing the scaling difficulty in terms of energy cost and reliability, some nonvolatile storage materials were proposed to be the substitute or supplement of main memory. Phase Change Memory (PCM) is one of the most promising nonvolatile memory that could be put into use in the near future. However, before becoming a qualified main memory technology, PCM should be designed reliably so that it can ensure the computer system's stable running even when errors occur. The typical wear-out errors in PCM have been well studied, but the transient errors, that caused by high-energy particles striking on the complementary metal-oxide semiconductor (CMOS) circuit of PCM chips or by resistance drifting in multi-level cell PCM, have attracted little focus. In this paper, we propose an innovative mechanism, Local-ECC-Global-ECPs (LEGE), which addresses both soft errors and hard errors (wear-out errors) in PCM memory systems. Our idea is to deploy a local error correction code (ECC) section to every data line, which can detect and correct one-bit errors immediately, and a global error correction pointers (ECPs) buffer for the whole memory chip, which can be reloaded to correct more hard error bits. The local ECC is used to detect and correct the unknown one-bit errors, and the global ECPs buffer is used to store the corrected value of hard errors. In comparison to ECP-6, our method provides almost identical lifetimes, but reduces approximately 50% storage overhead. Moreover, our structure reduces approximately 3.55% access latency overhead by increasing 1.61% storage overhead compared to PAYG, a hard error only solution