c-Abl downregulates the slow phase of double-strand break repair

c-Abl tyrosine kinase is activated by agents that induce double-strand DNA breaks (DSBs) and interacts with key components of the DNA damage response and of the DSB repair machinery. However, the functional significance of c-Abl in these processes, remained unclear. In this study, we demonstrate, using comet assay and pulsed-field gel electrophoresis, that c-Abl inhibited the repair of DSBs induced by ionizing radiation, particularly during the second and slow phase of DSB repair. Pharmacological inhibition of c-Abl and c-Abl depletion by siRNA-mediated knockdown resulted in higher DSB rejoining. c-Abl null MEFs exhibited higher DSB rejoining compared with cells reconstituted for c-Abl expression. Abrogation of c-Abl kinase activation resulted in higher H2AX phosphorylation levels and higher numbers of post-irradiation γH2AX foci, consistent with a role of c-Abl in DSB repair regulation. In conjunction with these findings, transient abrogation of c-Abl activity resulted in increased cellular radioresistance. Our findings suggest a novel function for c-Abl in inhibition of the slow phase of DSB repair

Adsorption and reduction of palladium (Pd2+) by Bacillus licheniformis R08

Preliminary study on the mechanism of Pd2+ biosorption by resting cells of Bacillus licheniformis R08 biomass has been carried out by means of chemical kinetics and AAS, TEM, XRD and FTIR methods. The results showed that at 30degreesC and PH 3.5, when dry R08 biomass powder (800 mg/L) was mixed with Pd2+ (100 mg/L) for 45 min, the rate constant k of biosorption of Pd2+ attained a maximum of 5.97 x 10(-2) min(-1) and the half life period of the reaction reached 12 min. The part of Pd2+ adsorbed by R08 biomass was reduced to elemental, cell-bound Pd-0 at the same condition. The cell wall of R08 biomass was the primary location for accumulating Pd2+, and aldoses, i. e. hydrolysate of a part of polysaccharides on the peptidoglycan layer in the acidic medium, serving as the electron donor, in situ reduced the Pd2+ to Pd-0

Temperature Dependence of Photoelectrical Properties of Single Selenium Nanowires

Influence of temperature on photoconductivity of single Se nanowires has been studied. Time response of photocurrent at both room temperature and low temperature suggests that the trap states play an important role in the photoelectrical process. Further investigations about light intensity dependence on photocurrent at different temperatures reveal that the trap states significantly affect the carrier generation and recombination. This work may be valuable for improving the device optoelectronic performances by understanding the photoelectrical properties

Impacts of Coulomb Interactions on the Magnetic Responses of Excitonic Complexes in Single Semiconductor Nanostructures

We report on the diamagnetic responses of different exciton complexes in single InAs/GaAs self-assembled quantum dots (QDs) and quantum rings (QRs). For QDs, the imbalanced magnetic responses of inter-particle Coulomb interactions play a crucial role in the diamagnetic shifts of excitons (X), biexcitons (XX), and positive trions (X−). For negative trions (X−) in QDs, anomalous magnetic responses are observed, which cannot be described by the conventional quadratic energy shift with the magnetic field. The anomalous behavior is attributed to the apparent change in the electron wave function extent after photon emission due to the strong Coulomb attraction by the hole in its initial state. In QRs, the diamagnetic responses of X and XX also show different behaviors. Unlike QDs, the diamagnetic shift of XX in QRs is considerably larger than that of X. The inherent structural asymmetry combined with the inter-particle Coulomb interactions makes the wave function distribution of XX very different from that of X in QRs. Our results suggest that the phase coherence of XX in QRs may survive from the wave function localization due to the structural asymmetry or imperfections

The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC

Dark matter scenarios in the minimal SUSY B-L model

We perform a study of the dark matter candidates of a constrained version of the minimal R-parity-conserving supersymmetric model with a gauged $U(1)_{B-L}$. It turns out that there are four additional candidates for dark matter in comparison to the MSSM: two kinds of neutralino, which either correspond to the gaugino of the $U(1)_{B-L}$ or to a fermionic bilepton, as well as "right-handed" CP-even and -odd sneutrinos. The correct dark matter relic density of the neutralinos can be obtained due to different mechanisms including new co-annihilation regions and resonances. The large additional Yukawa couplings required to break the $U(1)_{B-L}$ radiatively often lead to large annihilation cross sections for the sneutrinos. The correct treatment of gauge kinetic mixing is crucial to the success of some scenarios. All candidates are consistent with the exclusion limits of Xenon100.Comment: 45 pages, 22 figures; v2: extended discussion of direct detection cross section, matches published versio

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Nanogrids and Beehive-Like Nanostructures Formed by Plasma Etching the Self-Organized SiGe Islands

A lithography-free method for fabricating the nanogrids and quasi-beehive nanostructures on Si substrates is developed. It combines sequential treatments of thermal annealing with reactive ion etching (RIE) on SiGe thin films grown on (100)-Si substrates. The SiGe thin films deposited by ultrahigh vacuum chemical vapor deposition form self-assembled nanoislands via the strain-induced surface roughening (Asaro-Tiller-Grinfeld instability) during thermal annealing, which, in turn, serve as patterned sacrifice regions for subsequent RIE process carried out for fabricating nanogrids and beehive-like nanostructures on Si substrates. The scanning electron microscopy and atomic force microscopy observations confirmed that the resultant pattern of the obtained structures can be manipulated by tuning the treatment conditions, suggesting an interesting alternative route of producing self-organized nanostructures

How does our motor system determine its learning rate?

Motor learning is driven by movement errors. The speed of learning can be quantified by the learning rate, which is the proportion of an error that is corrected for in the planning of the next movement. Previous studies have shown that the learning rate depends on the reliability of the error signal and on the uncertainty of the motor system’s own state. These dependences are in agreement with the predictions of the Kalman filter, which is a state estimator that can be used to determine the optimal learning rate for each movement such that the expected movement error is minimized. Here we test whether not only the average behaviour is optimal, as the previous studies showed, but if the learning rate is chosen optimally in every individual movement. Subjects made repeated movements to visual targets with their unseen hand. They received visual feedback about their endpoint error immediately after each movement. The reliability of these error-signals was varied across three conditions. The results are inconsistent with the predictions of the Kalman filter because correction for large errors in the beginning of a series of movements to a fixed target was not as fast as predicted and the learning rates for the extent and the direction of the movements did not differ in the way predicted by the Kalman filter. Instead, a simpler model that uses the same learning rate for all movements with the same error-signal reliability can explain the data. We conclude that our brain does not apply state estimation to determine the optimal planning correction for every individual movement, but it employs a simpler strategy of using a fixed learning rate for all movements with the same level of error-signal reliability