Electron attachment to valence-excited CO

The possibility of electron attachment to the valence $^{3}\Pi$ state of CO is examined using an {\it ab initio} bound-state multireference configuration interaction approach. The resulting resonance has $^{4}\Sigma^{-}$ symmetry; the higher vibrational levels of this resonance state coincide with, or are nearly coincident with, levels of the parent $a^{3}\Pi$ state. Collisional relaxation to the lowest vibrational levels in hot plasma situations might yield the possibility of a long-lived CO$^-$ state.Comment: Revtex file + postscript file for one figur

Deregulation of the endogenous C/EBPβ LIP isoform predisposes to tumorigenesis

Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPbeta) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPbeta mRNA. The truncated C/EBPbeta LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPbeta LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPbeta knockin mice that constitutively express only the C/EBPbeta LIP isoform from its own locus. Our data show that deregulated C/EBPbeta LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPbeta LIP supports a pro-tumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/EBPbeta LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPbeta LIP isoform. KEY MESSAGE: Elevated C/EBPbeta LIP promotes cancer in mice. C/EBPbeta LIP is upregulated in B-NHL. Deregulated C/EBPbeta LIP alters apoptosis and cytokine/chemokine networks. Deregulated C/EBPbeta LIP may support a pro-tumorigenic microenvironment

How robust are future projections of forest landscape dynamics? Insights from a systematic comparison of four forest landscape models

Projections of landscape dynamics are uncertain, partly due to uncertainties in model formulations. However, quantitative comparative analyses of forest landscape models are lacking. We conducted a systematic comparison of all forest landscape models currently applied in temperate European forests (LandClim, TreeMig, LANDIS-II, iLand). We examined the uncertainty of model projections under several future climate, disturbance, and dispersal scenarios, and quantified uncertainties by variance partitioning. While projections under past climate conditions were in good agreement with observations, uncertainty under future climate conditions was high, with between-model biomass differences of up to 200 t ha−1. Disturbances strongly influenced landscape dynamics and contributed substantially to uncertainty in model projections (~25–40% of observed variance). Overall, model differences were the main source of uncertainty, explaining at least 50% of observed variance. We advocate a more rigorous and systematic model evaluation and calibration, and a broader use of ensemble projections to quantify uncertainties in future landscape dynamics

Reaction rates for Neutron Capture Reactions to C-, N- and O-isotopes to the neutron rich side of stability

The reaction rates of neutron capture reactions on light nuclei are important for reliably simulating nucleosynthesis in a variety of stellar scenarios. Neutron capture reaction rates on neutron-rich C-, N-, and O-isotopes are calculated in the framework of a hybrid compound and direct capture model. The results are tabulated and compared with the results of previous calculations as well as with experimental results.Comment: 33 pages (uses revtex) and 9 postscript figures, accepted for publication in Phys. Rev.

The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK

Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

"Activated" STAT Proteins: A Paradoxical Consequence of Inhibited JAK-STAT Signaling in Cytomegalovirus-Infected Cells

We have previously characterized mouse CMV (MCMV)–encoded immune-evasive IFN signaling inhibition and identified the viral protein pM27 as inducer of proteasomal degradation of STAT2. Extending our analysis to STAT1 and STAT3, we found that MCMV infection neither destabilizes STAT1 protein nor prevents STAT1 tyrosine Y701 phosphorylation, nuclear translocation, or the capability to bind g-activated sequence DNA-enhancer elements. Unexpectedly, the analysis of STAT3 revealed an induction of STAT3 Y705 phosphorylation by MCMV. In parallel, we found decreasing STAT3 protein amounts upon MCMV infection, although STAT3 expression normally is positive autoregulative. STAT3 phosphorylation depended on the duration of MCMV infection, the infectious dose, and MCMV gene expression but was independent of IFNAR1, IL-10, IL-6, and JAK2. Although STAT3 phosphorylation did not require MCMV immediate early 1, pM27, and late gene expression, it was restricted to MCMV- infected cells and not transmitted to bystander cells. Despite intact STAT1 Y701 phosphorylation, IFN-g–induced target gene transcription (e.g., IRF1 and suppressor of cytokine signaling [SOCS] 1) was strongly impaired. Likewise, the induction of STAT3 target genes (e.g., SOCS3) by IL-6 was also abolished, indicating that MCMV antagonizes STAT1 and STAT3 despite the occur- rence of tyrosine phosphorylation. Consistent with the lack of SOCS1 induction, STAT1 phosphorylation was prolonged upon IFN-g treatment. We conclude that the inhibition of canonical STAT1 and STAT3 target gene expression abrogates their intrinsic negative feedback loops, leading to accumulation of phospho–tyrosine-STAT3 and prolonged STAT1 phosphorylation. These findings challenge the generalization of tyrosine-phosphorylated STATs necessarily being transcriptional active and document antagonistic effects of MCMV on STAT1/3-dependent target gene expression

Geometry of Time and Dimensionality of Space

One of the most distinguished features of our algebraic geometrical, pencil concept of space-time is the fact that spatial dimensions and time stand, as far as their intrinsic structure is concerned, on completely different footings: the former being represented by pencils of lines, the latter by a pencil of conics. As a consequence, we argue that even at the classical (macroscopic) level there exists a much more intricate and profound coupling between space and time than that dictated by (general) relativity theory. It is surmised that this coupling can be furnished by so-called Cremona (or birational) transformations between two projective spaces of three dimensions, being fully embodied in the structure of configurations of their fundamental elements. We review properties of some of the simplest Cremona transformations and show that the corresponding "fundamental" space-times exhibit an intimate connection between the extrinsic geometry of time dimension and the dimensionality of space. Moreover, these Cremonian space-times seem to provide us with a promising conceptual basis for the possible reconciliation between two extreme concepts of (space-)time, viz. physical and psychological. Some speculative remarks in this respect are made

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype