Cug2 is essential for normal mitotic control and CNS development in zebrafish.

Background: We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2), which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models. Results: To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate. Conclusions: Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders

Suppression of allograft rejection with FK506: I. prolonged cardiac and liver survival in rats following short-course therapy

Heterotopic heart and orthotopic liver grafts from ACI donors were transplanted to Lewis rat recipients that were treated with a 3 (or 4) day course of FK506 IM that was started on postoperative day 0, 2, 3, 4, 5, or 6. Hearts, which rejected after a median of 6 days in untreated controls, always had prolonged survival (median 91 days) when treatment was started on postoperative day 4. The results were inferior when treatment was started earlier or later than this, but even when the first dose of FK506 was on postoperative day 5, one day before rejection was imminent in controls, the median survival was 50 days. The poorest results with a median graft survival of only 36 days were obtained when injections were on days 0–3. Results were similar with liver grafts that rejected after a median time of 10 days in nontreated controls but that usually survived permanently after a 3 (or 4) day FK506 course starting on day 0, 2, 3, or 4. Therapy started on day 6 was too late. © 1990 by Williams & Wilkins

Proportional-Integral Degradation (PI-Deg) control allows accurate tracking of biomolecular concentrations with fewer chemical reactions

We consider the design of synthetic embedded feedback circuits that can implement desired changes in the concentration of the output of a biomolecular process (reference tracking in control terminology). Such systems require the use of a "subtractor", to generate an error signal that captures the difference between the current and desired value of the process output. Unfortunately, standard implementations of the subtraction operator using chemical reaction networks are one-sided, i.e. they cannot produce negative error signals. Previous attempts to deal with this problem by representing signals as the difference in concentrations of two different biomolecular species lead to a doubling of the number of chemical reactions required to generate the circuit, hence sharply increasing the difficulty of experimental implementations and limiting the complexity of potential designs. Here we propose an alternative approach that introduces a degradation term into the classical proportion-integral control scheme. The extra tuning flexibility of the resulting PI-Deg controller compensates for the limitations of the one-sided subtraction operator, providing robust high-performance tracking of concentration changes with a minimal number of chemical reactions

System identification of gene regulatory networks for perturbation mitigation via feedback control

In Synthetic Biology, the idea of using feedback control for the mitigation of perturbations to gene regulatory networks due to disease and environmental disturbances is gaining popularity. To facilitate the design of such synthetic control circuits, a suitable model that captures the relevant dynamics of the gene regulatory network is essential. Traditionally, Michaelis-Menten models with Hill-type nonlinearities have often been used to model gene regulatory networks. Here, we show that such models are not suitable for the purposes of controller design, and propose an alternative formalism. Using tools from system identification, we show how to build so-called S-System models that capture the key dynamics of the gene regulatory network and are suitable for controller design. Using the identified S-System model, we design a genetic feedback controller for an example gene regulatory network with the objective of rejecting an external perturbation. Using a sine sweeping method, we show how the S-System model can be approximated by a second order linear transfer function and, based on this transfer function, we design our controller. Simulation results using the full nonlinear S-System model of the network show that the designed controller is able to mitigate the effect of external perturbations. Our findings highlight the usefulness of the S-System modelling formalism for the design of synthetic control circuits for gene regulatory networks

UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

All-Optical Ultrafast Control and Read-Out of a Single Negatively Charged Self-Assembled InAs Quantum Dot

We demonstrate the all-optical ultrafast manipulation and read-out of optical transitions in a single negatively charged self-assembled InAs quantum dot, an important step towards ultrafast control of the resident spin. Experiments performed at zero magnetic field show the excitation and decay of the trion (negatively charged exciton) as well as Rabi oscillations between the electron and trion states. Application of a DC magnetic field perpendicular to the growth axis of the dot enables observation of a complex quantum beat structure produced by independent precession of the ground state electron and the excited state heavy hole spins

Discovery of Trichopria keralensis (Hymenoptera, Diaprioidea, Diapriidae) in South Korea and Japan, a review of the keralensis species group of Trichopria and the nomenclature and synonymy of Alareka

Copyright Chang-Jun Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article