Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal-epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells

Endoplasmic reticulum protein 29 (ERp29) is a novel endoplasmic reticulum ( ER) secretion factor that facilitates the transport of secretory proteins in the early secretory pathway. Recently, it was found to be overexpressed in several cancers; however, little is known regarding its function in breast cancer progression. In this study, we show that the expression of ERp29 was reduced with tumor progression in clinical specimens of breast cancer, and that overexpression of ERp29 resulted in G(0)/G(1) arrest and inhibited cell proliferation in MDA-MB-231 cells. Importantly, overexpression of ERp29 in MDA-MB-231 cells led to a phenotypic change and mesenchymal-epithelial transition (MET) characterized by cytoskeletal reorganization with loss of stress fibers, reduction of fibronectin (FN), reactivation of epithelial cell marker E-cadherin and loss of mesenchymal cell marker vimentin. Knockdown of ERp29 by shRNA in MCF-7 cells reduced E-cadherin, but increased vimentin expression. Furthermore, ERp29 overexpression in MDA-MB-231 and SKBr3 cells decreased cell migration/invasion and reduced cell transformation, whereas silencing of ERp29 in MCF-7 cells enhanced cell aggressive behavior. Significantly, expression of ERp29 in MDA-MB-231 cells suppressed tumor formation in nude mice by repressing the cell proliferative index (Ki-67 positivity). Transcriptional profiling analysis showed that ERp29 acts as a central regulator by upregulating a group of genes with tumor suppressive function, for example, E-cadherin (CDH1), cyclin-dependent kinase inhibitor (CDKN2B) and spleen tyrosine kinase (SYK), and by downregulating a group of genes that regulate cell proliferation (eg, FN, epidermal growth factor receptor ( EGFR) and plasminogen activator receptor ( uPAR)). It is noteworthy that ERp29 significantly attenuated the overall ERK cascade, whereas the ratio of p-ERK1 to p-ERK2 was highly increased. Taken together, our results showed that ERp29 is a novel regulator leading to cell growth arrest and cell transition from a proliferative to a quiescent state, and reprogramming molecular portraits to suppress the tumor growth of MDA-MB-231 breast cancer cells. Laboratory Investigation (2009) 89, 1229-1242; doi: 10.1038/labinvest.2009.87; published online 21 September 2009

Ground state of low-dimensional dipolar gases: Linear and zigzag chains

We study the ground-state phase diagram of ultracold dipolar gases in highly anisotropic traps. Starting from a one-dimensional geometry, by ramping down the transverse confinement along one direction, the gas reaches various planar distributions of dipoles. At large linear densities, when the dipolar gas exhibits a crystal-like phase, critical values of the transverse frequency exist below which the configuration exhibits transverse patterns. These critical values are found by means of a classical theory, and are in full agreement with classical Monte Carlo simulations. The study of the quantum system is performed numerically with Monte Carlo techniques and shows that the quantum fluctuations smoothen the transition and make it completely disappear in a gas phase. These predictions could be experimentally tested and would allow one to reveal the effect of zero-point motion on self-organized mesoscopic structures of matter waves, such as the transverse pattern of the zigzag chain.

The first structural characterization of a [2.2]PHANEPHOS - Transition-metal complex: Structure of rac-[Pd(4,12-bis(diphenylphosphino)[2.2]paracyclophane)Cl-2]

The solid-state structure of the [2.2]PHANEPHOS-transition-metal complex rac-[Pd(4,12-bis(diphenylphosphino)[2.2]paracyclophane)Cl-2] has been established by single-crystal X-ray diffraction. The P-Pd-P bite angle is ideally suited to catalytic processes such as carbon-carbon cross-coupling reactions, which involve reductive elimination as the rate-determining step.

TIME-RESOLVED ABSORPTION, INFRARED, AND RESONANCE RAMAN-SPECTRA OF THE COMPLEXES [RU(X)(R)(CO)(2)(ALPHA-DIIMINE)] (X=HALIDE R=ALKYL) - INFLUENCE OF X ON THE CHARGE-TRANSFER CHARACTER OF THE LOWEST EXCITED-STATE

Nanosecond time-resolved absorption (TA), resonance Raman (TR(3)), and infrared (TRIR) spectra are reported for several complexes [Ru(X)(R)(CO)(2)(alpha-diimine)] (X = Cl, Br, I; R = Me, Et; alpha-diimine = N,N'-diisopropyl-1,4-diaza-1,3-butadiene (iPr-DAB), pyridine-2-carbaldehyde-N-isopropylimine (iPr-PyCa), 2,2'-bipyridine (bpy)). This is the first instance in which the TA, TR(3), and TRIR techniques have been used to probe excited states in the same series of complexes. The TA spectra of the iodide complexes show a transient absorption between 550 and 700 nm, which does not depend on the solvent but shifts to lower energy in the order iPr-DAB > bpy > iPr-PyCa. This band is assigned to an intraligand transition. For the corresponding chloride and bromide complexes this band occurs at higher energy, most probably because of a change of character of the lowest excited state from XLCT to MLCT. The TRIR spectra show an increase in v(CO) (and k(CO)) on promotion to the excited state; however, the shifts Delta v(CO) show a decrease in the order Cl- > Br- > I-. The TR(3) spectra of the excited complexes [Ru(X)(R)(Co)(2)(iPr-DAB)] show v(s)(CN) of the iPr-DAB ligand 50-80 cm(-1) lower in frequency than for the complexes in their ground state. This frequency shift decreases in the order Cl- > Br- > I-, indicating a decrease of CT character of the lowest excited state in this order. However, going from X = Br to I, the effect on Delta v(CO) is much larger than the decrease of Delta v(s)(CN). This different effect on the CO- and CN-stretching frequencies is assigned to a gradual change in character of the lowest excited state from MLCT to XLCT when Cl- is replaced by Br- and I-. This result confirms a similar conclusion derived from previous resonance Raman and emission experiments on these complexes.

Decay of Cystalline Order and Equilibration during the Solid-to-Plasma Transition Induced by 20-fs Microfocused 92-eV Free-Electron-Laser Pulses

We have studied a solid-to-plasma transition by irradiating Al foils with the FLASH free electron laser at intensities up to 10(16) W/cm(2). Intense XUV self-emission shows spectral features that are consistent with emission from regions of high density, which go beyond single inner-shell photoionization of solids. Characteristic features of intrashell transitions allowed us to identify Auger heating of the electrons in the conduction band occurring immediately after the absorption of the XUV laser energy as the dominant mechanism. A simple model of a multicharge state inverse Auger effect is proposed to explain the target emission when the conduction band at solid density becomes more atomiclike as energy is transferred from the electrons to the ions. This allows one to determine, independent of plasma simulations, the electron temperature and density just after the decay of crystalline order and to characterize the early time evolution.

The contribution of the United Nations Convention on the Rights of the Child to understanding and promoting the interests of young people making the transition from care to adulthood

The United Nations Convention on the Rights of the Child (UNCRC) acknowledges that young people without parental care are entitled to special support and assistance from the State. In detailing their expectations, the UN Committee have issued Guidelines for the Alternative Care of Children which recognise that State parties have a number of responsibilities towards care leavers. The paper explores how the UNCRC reporting process, and guidelines from the Committee outlining how States should promote the rights of young people making the transition from care to adulthood, can be used as an instrument to track global patterns of change in policy and practice. Content analysis of State Party Reports and Concluding Observations from 15 countries reveals that to date there has been limited engagement with understanding and promoting the needs of this group in the reporting process; although where a government is committed to developing legislation and practice then this does find its way into their national reports. Data supplied by affiliates of the International Research Network on Transitions to Adulthood from Care (INTRAC) reveals that national concerns, political ideology, public awareness, attitudes and knowledge of the vulnerability of care leavers influence service responses to protect and promote the rights of this group and the attention afforded to such issues in reports to the Committee. Findings also suggest that global governance is not simply a matter of top down influence. Future work on both promoting and monitoring of the impact of the UNCRC needs to recognise that what is in play is the management of a complex global/national dynamic with all its uneven development, levels of influence and with a range of institutional actors involved.

Amnesties in Transition: Punishment, Restoration, and the Governance of Mercy

Despite the much vaunted triumph of human rights, amnesties continue to be a frequently used technique of post-conflict transitional justice. For many critics, they are synonymous with unaccountability and injustice. This article argues that despite the rhetoric, there is no universal duty to prosecute under international law and that issues of selectivity and proportionality present serious challenges to the retributive rationale for punishment in international justice. It contends that many of the assumptions concerning the deterrent effect in the field are also oversold and poorly theorized. It also suggests that appropriately designed restorative amnesties can be both lawful and effective as routes to truth recovery, reconciliation, and a range of other peacemaking goals. Rather than mere instruments of impunity, amnesties should instead be seen as important institutions in the governance of mercy, the reassertion of state sovereignty and, if properly constituted, the return of law to a previously lawless domain.

The transition to agriculture

Malone, C.A.T.,, in, C. Malone and S. Stoddart, (eds.). 1994, Cambridge University Press: Cambridge. p. 67-

Characterisation of the active/de-active transition of mitochondrial complex I

Oxidation of NADH in the mitochondrial matrix of aerobic cells is catalysed by mitochondrial complex I. The regulation of this mitochondrial enzyme is not completely understood. An interesting characteristic of complex I from some organisms is the ability to adopt two distinct states: the so-called catalytically active (A) and the de-active, dormant state (D). The A-form in situ can undergo de-activation when the activity of the respiratory chain is limited (i.e. in the absence of oxygen). The mechanisms and driving force behind the A/D transition of the enzyme are currently unknown, but several subunits are most likely involved in the conformational rearrangements: the accessory subunit 39 kDa (NDUFA9) and the mitochondrially encoded subunits, ND3 and ND1. These three subunits are located in the region of the quinone binding site. The A/D transition could represent an intrinsic mechanism which provides a fast response of the mitochondrial respiratory chain to oxygen deprivation. The physiological role of the accumulation of the D-form in anoxia is most probably to protect mitochondria from ROS generation due to the rapid burst of respiration following reoxygenation. The de-activation rate varies in different tissues and can be modulated by the temperature, the presence of free fatty acids and divalent cations, the NAD/NADH ratio in the matrix, the presence of nitric oxide and oxygen availability. Cysteine-39 of the ND3 subunit, exposed in the D-form, is susceptible to covalent modification by nitrosothiols, ROS and RNS. The D-form in situ could react with natural effectors in mitochondria or with pharmacological agents. Therefore the modulation of the re-activation rate of complex I could be a way to ameliorate the ischaemia/reperfusion damage. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira.

Pyroelectric and piezoelectric scanning microscopy applied to reveal the bipolar state of 4-iodo-4 '-nitrobiphenyl (INBP)

Two recent scanning probe techniques were applied to investigate the bipolar twin state of 4-iodo-4'-nitrobiphenyl (INBP) crystals. Solution grown crystals of INBP show typically a morphology which does not express that of a mono-domain polar structure (Fdd2, mm2). From previous X-ray diffraction a twinning volume ratio of similar to 70 : 30 is now explained by two unipolar domains (Flack parameter: 0.075(29)) of opposite orientation of the molecular dipoles, joined by a transition zone showing a width of similar to 140 mm. Scanning pyroelectric microscopy (SPEM) demonstrates a continuous transition of the polarization P from +P into -P across the zone. Application of piezoelectric force microscopy (PFM) confirms unipolar alignment of INBP molecules down to a resolution of similar to 20 nm. A previously proposed real structure for INBP crystals built from lamellae with antiparallel alignment is thus rejected. Anomalous X-ray scattering was used to determine the absolute molecular orientation in the two domains. End faces of the polar axis 2 are thus made up by NO2 groups. Using a previously determined negative pyroelectric coefficient pc leads to a confirmation also by a SPEM analysis. Calculated values for functional group interactions (D...A), (A...A), (D...D) and the stochastic theory of polarity formation allow us to predict that NO2 groups should terminate corresponding faces. Following the present analysis, INBP may represent a first example undergoing dipole reversal upon growth to end up in a bipolar state.

Long-range multipartite entanglement close to a first-order quantum phase transition

We provide insight into the quantum correlations structure present in strongly correlated systems beyond the standard framework of bipartite entanglement. To this aim we first exploit rotationally invariant states as a test bed to detect genuine tripartite entanglement beyond the nearest neighbor in spin-1/2 models. Then we construct in a closed analytical form a family of entanglement witnesses which provides a sufficient condition to determine if a state of a many-body system formed by an arbitrary number of spin-1/2 particles possesses genuine tripartite entanglement, independently of the details of the model. We illustrate our method by analyzing in detail the anisotropic XXZ spin chain close to its phase transitions, where we demonstrate the presence of long-range multipartite entanglement near the critical point and the breaking of the symmetries associated with the quantum phase transition.

Evidence for a glassy state in strongly driven carbon

Here, we report results of an experiment creating a transient, highly correlated carbon state using a combination of optical and x-ray lasers. Scattered x-rays reveal a highly ordered state with an electrostatic energy significantly exceeding the thermal energy of the ions. Strong Coulomb forces are predicted to induce nucleation into a crystalline ion structure within a few picoseconds. However, we observe no evidence of such phase transition after several tens of picoseconds but strong indications for an over-correlated fluid state. The experiment suggests a much slower nucleation and points to an intermediate glassy state where the ions are frozen close to their original positions in the fluid.

Investigation of the solid-liquid phase transition of carbon at 150 GPa with spectrally resolved X-ray scattering

We have resolved the solid-liquid phase transition of carbon at pressures around 150GPa. High-pressure samples of different temperatures were created by laser-driven shock compression of graphite and varying the initial density from 1.30g/cm³ to 2.25g/cm³. In this way, temperatures from 5700K to 14,500K could be achieved for relatively constant pressure according to hydrodynamic simulations. From measuring the elastic X-ray scattering intensity of vanadium K-alpha radiation at 4.95keVat a scattering angle of 126°, which is very sensitive to the solid-liquid transition, we can determine whether the sample had transitioned to the fluid phase. We find that samples of initial density 1.3g/cm³ and 1.85g/cm³ are liquid in the compressed states, whereas samples close to the ideal graphite crystal density of 2.25g/cm³ remain solid, probably in a diamond-like state.

Transitional Justice: Conceptualising 'Transition'

Scholars and practitioners working in ‘transitional justice’ are concerned with remedies of accountability and redress in the aftermath of conflict and state repression. Transitional justice, it is argued, provides recognition of the rights of victims, promotes civic trust, and strengthens the democratic rule of law. As serious scholarship flourishes around this critical concept as never before, this new collection from Routledge meets the need for an authoritative reference work to map a vibrant site of research and reflection. In four volumes, Transitional Justice brings together foundational and the best and most influential cutting-edge materials, including key works produced before the term ‘transitional justice’ gained wide currency but which anticipate approaches now included under that rubric.

The collection covers themes such as: truth and history; acknowledgement, reconciliation, and forgiveness; retribution, restorative justice and reparations; and democracy, state-building, identity, and civil society

Understanding Young People’s Transitions from State Care: the need for connections,

Over the last decade in a growing number of countries there has emerged an interest in the experiences of young people leaving state care. This has included a limited amount of cross national comparison. This paper reports the bleak descriptive picture of poor outcomes and lack of support that has emerged
but cautions that this be recognised as primarily expressing an Anglo-American descriptive empirical engagement with the issue. It then goes on to argue for using Esping-Anderson’s three types of welfare regime and the European Union policy goal of social inclusion as starting points to develop a more dynamic, systemic international picture of care leaving.