Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release

Poly(ADP-ribose) polymerase-1-dependent cell death (known as parthanatos) plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor), but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate) treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders

A 10-year record of Arctic summer sea ice freeboard from CryoSat-2

Satellite observations of pan-Arctic sea ice thickness have so far been constrained to winter months. For radar altimeters, conventional methods cannot differentiate leads from meltwater ponds that accumulate at the ice surface in summer months, which is a critical step in the ice thickness calculation. Here, we use over 350 optical and synthetic aperture radar (SAR) images from the summer months to train a 1D convolution neural network for separating CryoSat-2 radar altimeter returns from sea ice floes and leads with an accuracy >80%. This enables us to generate the first pan-Arctic measurements of sea ice radar freeboard for May–September between 2011 and 2020. Results indicate that the freeboard distributions in May and September compare closely to those from a conventional ‘winter’ processor in April and October, respectively. The freeboards capture expected patterns of sea ice melt over the Arctic summer, matching well to ice draft observations from the Beaufort Gyre Exploration Program (BGEP) moorings. However, compared to airborne laser scanner freeboards from Operation IceBridge and airborne EM ice thickness surveys from the Alfred Wegener Institute (AWI) IceBird program, CryoSat-2 freeboards are underestimated by 0.02–0.2 m, and ice thickness is underestimated by 0.28–1.0 m, with the largest differences being over thicker multi-year sea ice. To create the first pan-Arctic summer sea ice thickness dataset we must address primary sources of uncertainty in the conversion from radar freeboard to ice thickness

Cysteine (C)-X-C Receptor 4 Undergoes Transportin 1-Dependent Nuclear Localization and Remains Functional at the Nucleus of Metastatic Prostate Cancer Cells

published_or_final_versio

Vulnerability and adaptation to extreme coastal flooding: An example from the south ford area, scottish outer hebrides

Vulnerability to climate change is a function of both exposure and sensitivity to the impacts of climate change and coping capacity, whether physical or human, to deal with those impacts. The coast is a dynamic environment where physical change is constant. Severe flooding and damage to land, property and coastal infrastructure in the Outer Hebrides of Scotland during January 2005 was caused by a highly destructive storm coupled with tidal surge and the cumulative impact of relative rising sea level. The impacts of the storm highlighted the vulnerability of coastal communities living on low-lying soft coasts and the need for an adaptive response in taking measures to protect them from the harmful effects of future storms. The purpose of this paper is to report on the changing approaches to coastal protection practices in the Outer Hebrides that have resulted from climate change adaptation research. The focus of the paper is on an area of intertidal sands between the islands of Benbecula and South Uist and the consequences of replacing an open span bridge with a rockfill causeway and the sea breaching a barrier island with the result of extensive coastal flooding experienced during the storm. CoastAdapt was a transnational project which aimed to develop adaptation strategies and tools to help people and authorities adopt measures in response to climate and environmental change. Using a participatory approach, a stepwise methodological approach to building local adaptive capacity was developed. In making recommendations for action in reducing the risk from flooding key measures arranged in terms of efficacy and affordability are listed in a hazard management matrix. These measures range from replacing a significant section of causeway with a bridge to inexpensive options such as dune management and improved flood warning. The process is transferable to a variety of coastal localities and situations and especially so given the need to balance the safeguarding of local coastal communities with agreement on cost effective and appropriate measures which address the growing impacts of climate change

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

Optical one-way quantum computing with a simulated valence-bond solid

One-way quantum computation proceeds by sequentially measuring individual spins (qubits) in an entangled many-spin resource state. It remains a challenge, however, to efficiently produce such resource states. Is it possible to reduce the task of generating these states to simply cooling a quantum many-body system to its ground state? Cluster states, the canonical resource for one-way quantum computing, do not naturally occur as ground states of physical systems. This led to a significant effort to identify alternative resource states that appear as ground states in spin lattices. An appealing candidate is a valence-bond-solid state described by Affleck, Kennedy, Lieb, and Tasaki (AKLT). It is the unique, gapped ground state for a two-body Hamiltonian on a spin-1 chain, and can be used as a resource for one-way quantum computing. Here, we experimentally generate a photonic AKLT state and use it to implement single-qubit quantum logic gates.Comment: 11 pages, 4 figures, 8 tables - added one referenc

The Hubble Space Telescope Cluster Supernova Survey: II. The Type Ia Supernova Rate in High-Redshift Galaxy Clusters

We report a measurement of the Type Ia supernova (SN Ia) rate in galaxy clusters at 0.9 < z < 1.45 from the Hubble Space Telescope (HST) Cluster Supernova Survey. This is the first cluster SN Ia rate measurement with detected z > 0.9 SNe. Finding 8 +/- 1 cluster SNe Ia, we determine a SN Ia rate of 0.50 +0.23-0.19 (stat) +0.10-0.09 (sys) SNuB (SNuB = 10^-12 SNe L_{sun,B}^-1 yr^-1). In units of stellar mass, this translates to 0.36 +0.16-0.13 (stat) +0.07-0.06 (sys) SNuM (SNuM = 10^-12 SNe M_sun^-1 yr^-1). This represents a factor of approximately 5 +/- 2 increase over measurements of the cluster rate at z < 0.2. We parameterize the late-time SN Ia delay time distribution with a power law (proportional to t^s). Under the assumption of a cluster formation redshift of z_f = 3, our rate measurement in combination with lower-redshift cluster SN Ia rates constrains s = -1.41 +0.47/-0.40, consistent with measurements of the delay time distribution in the field. This measurement is generally consistent with expectations for the "double degenerate" scenario and inconsistent with some models for the "single degenerate" scenario predicting a steeper delay time distribution at large delay times. We check for environmental dependence and the influence of younger stellar populations by calculating the rate specifically in cluster red-sequence galaxies and in morphologically early-type galaxies, finding results similar to the full cluster rate. Finally, the upper limit of one host-less cluster SN Ia detected in the survey implies that the fraction of stars in the intra-cluster medium is less than 0.47 (95% confidence), consistent with measurements at lower redshifts.Comment: 29 pages, 14 figures. Accepted for publication in ApJ on 16 February 2011. See the HST Cluster Supernova Survey website at http://supernova.lbl.gov/2009ClusterSurvey for a version with full-resolution images and a complete listing of transient candidates from the survey. This version fixes a typo in the metadata; the paper is unchanged from v

Exclusive Production of Higgs Bosons in Hadron Colliders

We study the exclusive, double--diffractive production of the Standard Model Higgs particle in hadronic collisions at LHC and FNAL (upgraded) energies. Such a mechanism would provide an exceptionally clean signal for experimental detection in which the usual penalty for triggering on the rare decays of the Higgs could be avoided. In addition, because of the color singlet nature of the hard interaction, factorization is expected to be preserved, allowing the cross--section to be related to similar hard--diffractive events at HERA. Starting from a Fock state expansion in perturbative QCD, we obtain an estimate for the cross section in terms of the gluon structure functions squared of the colliding hadrons. Unfortunately, our estimates yield a production rate well below what is likely to be experimentally feasible.Comment: 17 pages, RevTeX file, four uufiled PostScript figures. UMPP #94-177. (Revised version. Some mistakenly missing Feynman diagrams are now added. Results do not change qualitatively. Paper reorganized.

REDSHIFT MEASUREMENT and SPECTRAL CLASSIFICATION for eBOSS GALAXIES with the REDMONSTER SOFTWARE

We describe the redmonster automated redshift measurement and spectral classification software designed for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV). We describe the algorithms, the template standard and requirements, and the newly developed galaxy templates to be used on eBOSS spectra. We present results from testing on early data from eBOSS, where we have found a 90.5% automated redshift and spectral classification success rate for the luminous red galaxy sample (redshifts 0.6 ≲ z ≲ 1.0). The redmonster performance meets the eBOSS cosmology requirements for redshift classification and catastrophic failures and represents a significant improvement over the previous pipeline. We describe the empirical processes used to determine the optimum number of additive polynomial terms in our models and an acceptable δX2rthreshold for declaring statistical confidence. Statistical errors on redshift measurement due to photon shot noise are assessed, and we find typical values of a few tens of km s-1. An investigation of redshift differences in repeat observations scaled by error estimates yields a distribution with a Gaussian mean and standard deviation of μ ∼ 0.01 and σ ∼ 0.65, respectively, suggesting the reported statistical redshift uncertainties are over-estimated by ∼54%. We assess the effects of object magnitude, signal-to-noise ratio, fiber number, and fiber head location on the pipeline's redshift success rate. Finally, we describe directions of ongoing development