ALBERT

Description: The ataxia telangiectasia mutated and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) axis is the major signaling pathway activated in response to replication stress and is essential for the intra-S checkpoint. ATR phosphorylates and activates a number of molecules to coordinate cell cycle progression. Chk1 is the major effector downstream from ATR and plays a critical role in intra-S checkpoint on replication stress. Activation of Chk1 kinase also requires its association with Claspin, an adaptor protein essential for Chk1 protein stability, recruitment and ATR-dependent Chk1 phosphorylation. We have previously reported that, on replication stress, the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is rapidly phosphorylated by ATR at the stalled replication forks and is required for cellular resistance to replication stresses although the impact of DNA-PKcs onto the ATR signaling pathway remains elusive. Here we report that ATR-dependent Chk1 phosphorylation and Chk1 signaling are compromised in the absence of DNA-PKcs. Our investigation reveals that DNA-PKcs is required to maintain Chk1–Claspin complex stability and transcriptional regulation of Claspin expression. The impaired Chk1 activity results in a defective intra-S checkpoint response in DNA-PKcs–deficient cells. Taken together, these results suggest that DNA-PKcs, in addition to its direct role in DNA damage repair, facilitates ATR-Chk1 signaling pathway in response to replication stress.

Description: Using all the RXTE archival data of Sco X-1 and GX 5-1, which amount to about 1.6 Ms in total, we searched for possible occultation events caused by Oort Cloud objects. The detection efficiency of our searching approach was studied with simulation. Our search is sensitive to object size of about 300 m in the inner Oort Cloud, taking 4000 au as a representative distance, and of 900 m in the outer Oort Cloud, taking 36 000 au as the representative distance. No occultation events were found in the 1.6 Ms data. We derived upper limits to the number of Oort Cloud objects, which are about three orders of magnitude higher than the highest theoretical estimates in the literature for the inner Oort Cloud, and about six orders higher for the outer Oort Cloud. Although these upper limits are not constraining enough, they are the first obtained observationally, without making any model assumptions about comet injection. They also provide guidance to such serendipitous occultation event search in the future.

Description: Two methods for computing gravitational potential difference (GPD) between the GRACE satellites using orbit data have been formulated based on energy integral; one in geocentric inertial frame (GIF) and another in Earth fixed frame (EFF). Here we present a rigorous theoretical formulation in EFF with particular emphasis on necessary approximations, provide a computational approach to mitigate the approximations to negligible level, and verify our approach using simulations. We conclude that a term neglected or ignored in all former work without verification should be retained. In our simulations, 2 cycle per revolution (CPR) errors are present in the GPD computed using our formulation, and empirical removal of the 2 CPR and lower frequency errors can improve the precisions of Stokes coefficients (SCs) of degree 3 and above by 1–2 orders of magnitudes. This is despite of the fact that the result without removing these errors is already accurate enough. Furthermore, the relation between data errors and their influences on GPD is analysed, and a formal examination is made on the possible precision that real GRACE data may attain. The result of removing 2 CPR errors may imply that, if not taken care of properly, the values of SCs computed by means of the energy integral method using real GRACE data may be seriously corrupted by aliasing errors from possibly very large 2 CPR errors based on two facts: (1) errors of $\bar C_{2,0} $ manifest as 2 CPR errors in GPD and (2) errors of $\bar C_{2,0} $ in GRACE data—the differences between the CSR monthly values of $\bar C_{2,0} $ independently determined using GRACE and SLR are a reasonable measure of their magnitude—are very large. Our simulations show that, if 2 CPR errors in GPD vary from day to day as much as those corresponding to errors of $\bar C_{2,0} $ from month to month, the aliasing errors of degree 15 and above SCs computed using a month's GPD data may attain a level comparable to the magnitude of gravitational potential variation signal that GRACE was designed to recover. Consequently, we conclude that aliasing errors from 2 CPR errors in real GRACE data may be very large if not properly handled; and therefore, we propose an approach to reduce aliasing errors from 2 CPR and lower frequency errors for computing SCs above degree 2.

Description: In this paper, we consider a 1D wave equation with time delay in the information transmission in which the delay depends on position. We mainly discuss the solvability and stability of this time-delay system. Using the analytic method, we prove that if the largest time delay equals to 1, the system equation is insolvable in the sense of exponential bounded solution. If the largest time delay is not equal to 1, we prove that the system is always solvable by the Riesz basis approach. Further, we discuss the stability of this system when it is solvable. We show that if the delay time is smaller than 1 and the feedback gain constant also is small enough, the system is stable exponentially, and when delay is large or the gain constant is unsuitable, the system is unstable. In particular, we obtain a sufficient condition for the exponential stability of the system. Finally, we give some simulations for the stable region.

Description: Two exact formulae for the eigenvalues of one-dimensional wave equations on general feedback controlled networks are presented. Especially, by them together with the exponential polynomial theory and the graph theory, it is shown that the oscillation of tree-shaped networks with one fixed vertex can rest in finite time with appropriate dampers. In the end, the two concrete networks are given and their eigenvalues are calculated to demonstrate our theoretical results.

Description: Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen–host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus–animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.

Description: In this paper, we consider the stabilization problem for a wave equation with distributed controller delay. Suppose that the output of the boundary controller is of the form $\alpha u(t)+\beta u(t-\tau) +\int_{-\tau}^{0} g(\eta) u(t+\eta)\,{\rm d}\eta$ , where u ( t ) is the controller input, α , β R are two constants of the controller, 〉0 is the maximal time delay and g ( ) L 2 [– , 0] which does not equal zero. Using the tricks of the Luenberger observer and partial state predictor, the delayed system can be transformed to a system which has no time delay. Based on this system with no time delay, we deduce a kind of dynamic feedback control law that can exponentially stabilize the delayed system.

Description: Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20 –/– spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.