Aurora A kinase (AURKA) in normal and pathological cell division

Temporally and spatially controlled activation of the Aurora A kinase (AURKA) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis. Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis. These properties have led Aurora A to be considered a high-value target for development of cancer therapeutics, with multiple agents currently in early-phase clinical trials. More recently, identification of additional, non-mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors. Here we review the mitotic and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer.     

物质的演化——从宇宙大爆炸到现代地球

宇宙化学和地球化学在上一个20年里虽然已经取得了飞跃发展，但分支学科的细化使得研究在越来越深入的同时也变得越来越分散。许多研究论文不可避免地专注于某一分支的问题，而很少与主题相关的其它分支的工作有关联。本书由Tolstikhin博士和Kramers博士撰写，其难度介于教科书和专著之间，作者在阐述相关科学问题时，试图将专著的深度和教科书的广度完美地结合起来。     

Real-time quantum feedback prepares and stabilizes photon number states

Feedback loops are central to most classical control procedures. A controller compares the signal measured by a sensor (system output) with the target value or set-point. It then adjusts an actuator (system input) to stabilize the signal around the target value. Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback, which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system. An optimal compromise uses weak measurements, providing partial information with minimal perturbation. The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target. Although some aspects of this scenario have been experimentally demonstrated for the control of quantum or classical micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized. Here we have implemented such a real-time stabilizing quantum feedback scheme following a method inspired by ref. 13. It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps. The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number. The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements. The microwave field is a quantum oscillator usable as a quantum memory or as a quantum bus swapping information between atoms. Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence, and is a significant step towards the implementation of complex quantum information operations.     

Melatonin receptors limit dopamine reuptake by regulating dopamine transporter cell-surface exposure

Melatonin, a neuro-hormone released by the pineal gland, has multiple effects in the central nervous system including the regulation of dopamine (DA) levels, but how melatonin accomplishes this task is not clear. Here, we show that melatonin MT₁ and MT₂ receptors co-immunoprecipitate with the DA transporter (DAT) in mouse striatal synaptosomes. Increased DA re-uptake and decreased amphetamine-induced locomotor activity were observed in the striatum of mice with targeted deletion of MT₁ or MT₂ receptors. In vitro experiments confirmed the interactions and recapitulated the inhibitory effect of melatonin receptors on DA re-uptake. Melatonin receptors retained DAT in the endoplasmic reticulum in its immature non-glycosylated form. In conclusion, we reveal one of the first molecular complexes between G protein-coupled receptors (MT₁ and MT₂) and transporters (DAT) in which melatonin receptors regulate the availability of DAT at the plasma membrane, thus limiting the striatal DA re-uptake capacity in mice.     

The mesenchymoangioblast,mesodermal precursor for mesenchymal and endothelial cells

Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNR⁺PDGFRα⁺KDR⁺ mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβ⁺CD271⁺EMCN⁺DLK1⁺CD73^? primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3–4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.     

Improving the efficiency of transport systems using simulation

The article describes the possibilities of application of simulation modeling for the analysis of infrastructure and technology of transport services of enterprises. The main technological and possible economic effects for the enterprises arising at performance of modeling of a transport component of their work are resulted.     

Norm-based face encoding by single neurons in the monkey inferotemporal cortex

The rich and immediate perception of a familiar face, including its identity, expression and even intent, is one of the most impressive shared faculties of human and non-human primate brains. Many visually responsive neurons in the inferotemporal cortex of macaque monkeys respond selectively to faces, sometimes to only one or a few individuals, while showing little sensitivity to scale and other details of the retinal image. Here we show that face-responsive neurons in the macaque monkey anterior inferotemporal cortex are tuned to a fundamental dimension of face perception. Using a norm-based caricaturization framework previously developed for human psychophysics, we varied the identity information present in photo-realistic human faces, and found that neurons of the anterior inferotemporal cortex were most often tuned around the average, identity-ambiguous face. These observations are consistent with face-selective responses in this area being shaped by a figural comparison, reflecting structural differences between an incoming face and an internal reference or norm. As such, these findings link the tuning of neurons in the inferotemporal cortex to psychological models of face identity perception.     

Rapid freshening of the deep North Atlantic Ocean over the past four decades

The overflow and descent of cold, dense water from the sills of the Denmark Strait and the Faroe Shetland channel into the North Atlantic Ocean is the principal means of ventilating the deep oceans, and is therefore a key element of the global thermohaline circulation. Most computer simulations of the ocean system in a climate with increasing atmospheric greenhouse-gas concentrations predict a weakening thermohaline circulation in the North Atlantic as the subpolar seas become fresher and warmer, and it is assumed that this signal will be transferred to the deep ocean by the two overflows. From observations it has not been possible to detect whether the ocean's overturning circulation is changing, but recent evidence suggests that the transport over the sills may be slackening. Here we show, through the analysis of long hydrographic records, that the system of overflow and entrainment that ventilates the deep Atlantic has steadily changed over the past four decades. We find that these changes have already led to sustained and widespread freshening of the deep ocean.     

Pathogen-induced systemic plant signal triggers DNA rearrangements

Plant genome stability is known to be affected by various abiotic environmental conditions, but little is known about the effect of pathogens. For example, exposure of maize plants to barley stripe mosaic virus seems to activate transposable elements and to cause mutations in the non-infected progeny of infected plants. The induction by barley stripe mosaic virus of an inherited effect may mean that the virus has a non-cell-autonomous influence on genome stability. Infection with Peronospora parasitica results in an increase in the frequency of somatic recombination in Arabidopsis thaliana; however, it is unclear whether effects on recombination require the presence of the pathogen or represent a systemic plant response. It is also not clear whether the changes in the frequency of somatic recombination can be inherited. Here we report a threefold increase in homologous recombination frequency in both infected and non-infected tissue of tobacco plants infected with either tobacco mosaic virus or oilseed rape mosaic virus. These results indicate the existence of a systemic recombination signal that also results in an increased frequency of meiotic and/or inherited late somatic recombination.     

A change in the freshwater balance of the Atlantic Ocean over the past four decades

The oceans are a global reservoir and redistribution agent for several important constituents of the Earth's climate system, among them heat, fresh water and carbon dioxide. Whereas these constituents are actively exchanged with the atmosphere, salt is a component that is approximately conserved in the ocean. The distribution of salinity in the ocean is widely measured, and can therefore be used to diagnose rates of surface freshwater fluxes, freshwater transport and local ocean mixing--important components of climate dynamics. Here we present a comparison of salinities on a long transect (50 degrees S to 60 degrees N) through the western basins of the Atlantic Ocean between the 1950s and the 1990s. We find systematic freshening at both poleward ends contrasted with large increases of salinity pervading the upper water column at low latitudes. Our results extend a growing body of evidence indicating that shifts in the oceanic distribution of fresh and saline waters are occurring worldwide in ways that suggest links to global warming and possible changes in the hydrologic cycle of the Earth.