To ensure proper mitotic progression, robust ordering of the destruction of APC/CCdc20 substrates is driven by the integration of molecular mechanisms ranging from phosphorylation-dependent interaction with substrates to sensing of the status of the spindle assembly checkpoint.

Our data suggest that aPE may be a risk factor in patients with mid-to-late pregnancy loss(es) as well as recurrent early pregnancy losses.

Natural killer cells (NK cells) play an important role in innate immunity. NK cells recognize self and nonself depending on the balance of activating receptors and inhibitory receptors. After binding to their ligands, NK cell receptors trigger subsequent signaling conduction and then determine whether NK is activated or inhibited. Furthermore, NK cell response includes cytotoxicity and cytokine release, which is tightly related to the activation of NK cell-activating receptors and the inhibition of inhibitory receptors on the surfaces of NK cells. The expression and function of NK cell surface receptors also alter in virus infection, tumor, and autoimmune diseases and influence the occurrence and development of diseases. So, it is important to understand the mechanism of recognition between NK receptors and their ligands in pathological conditions and the signaling pathways of NK cell receptors. This review mainly summarizes the research progress on NK cell surface receptors and their signal pathways.

BackgroundDuring cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/CCdc20, a key regulator of chromosome segregation in mitosis.ResultsWe show experimentally that the rate of catalysis varies with different substrates of APC/CCdc20. Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/CCdc20 can alter the timing of degradation onset relative to APC/CCdc20 activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/CCdc20, their relative enzyme affinities and rates of catalysis influence the partitioning of APC/CCdc20 among substrates, resulting in substrate competition. Depending on how APC/CCdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/CCdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing.ConclusionsThe degradation timing of APC/CCdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/CCdc20 interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0205-6) contains supplementary material, which is available to authorized users.

An ultra-fast physical random number generator is demonstrated utilizing a photonic integrated device based broadband chaotic source with a simple post data processing method. The compact chaotic source is implemented by using a monolithic integrated dual-mode amplified feedback laser (AFL) with self-injection, where a robust chaotic signal with RF frequency coverage of above 50 GHz and flatness of ±3.6 dB is generated. By using 4-least significant bits (LSBs) retaining from the 8-bit digitization of the chaotic waveform, random sequences with a bit-rate up to 640 Gbit/s (160 GS/s × 4 bits) are realized. The generated random bits have passed each of the fifteen NIST statistics tests (NIST SP800-22), indicating its randomness for practical applications.