Stress precipitates functional deficits following striatal silent stroke: A synergistic effect

Stress has been linked to structural and functional outcomes after stroke. Moreover, the striatum, both dorsal and ventral, is a vital regulator of stress perception and associated physiological responses. This study investigates potential synergistic effects of focal stroke in the ventrolateral striatum and restraint stress on motor and spatial performance. Adult male Long-Evans rats were pre-trained in a skilled reaching task and randomly assigned to sham, stroke-only, stress-only and stroke. +. stress conditions. Ventrolateral striatal focal ischemia was induced by endothelin-1 (ET-1) infusion. Rats in stress-only and stroke. +. stress groups received 21. days of mild restraint stress after stroke. All rats were tested in the skilled reaching task and the ziggurat task (ZT) for post-stroke motor and spatial performance. There was no effect of ventrolateral striatal ischemia or stress alone on motor and spatial performance. Notably, stroke and stress interacted synergistically to reduce reaching success and to disrupt qualitative aspects of movement performance in the absence of histological differences in lesion size. Thus, stress can precipitate behavioural deficits after focal ischemia even in the absence of significant functional deficits on its own. These results emphasize the importance of prevention programmes to control post-stroke levels of stress in clinical populations. © 2011 Elsevier Inc

Stress after hippocampal stroke enhances spatial performance in rats

The nature of stress-related cognitive changes is still a matter of debate. Stress is often considered to be deleterious to cognitive function, despite many instances in which beneficial effects are evident in neural structure and cognition. Moreover, in some neuropathological conditions such as focal ischemia, stress exaggerates loss of cognitive function. The present experiments set out to investigate the effects of repeated restraint stress on spatial cognition in rats, and on recovery from a focal stroke induced by injection of endothelin-1 (ET-1) into the hippocampus (HPC). We did not observe a deleterious effect of stress on performance in the Morris water task (MWT). The HPC focal stroke induced by ET-1 produced lasting spatial learning impairments. Importantly, rats in the HPC stroke. +. stress group exhibited superior performance in the MWT compared with the HPC stroke-only group. No between-group structural difference was observed related to stress. These findings confirm that corticosterone-related experiences may be key factors influencing cognitive performance after HPC focal ischemic stroke. © 2010 Elsevier Inc

Chronic stress prior to hippocampal stroke enhances post-stroke spatial deficits in the ziggurat task

Stress is one of the most important variables to determine recovery following stroke. We have previously reported that post-stroke exposure to either stress or corticosterone (CORT) alleviates hippocampal ischemic outcome. The present experiment expands previous findings by investigating the influence of exposure to stress prior to ischemic event. Rats received either daily restraint stress (1. h/day; 16 consecutive days) or CORT (0.5. mg/kg; 16 consecutive days) prior to focal ischemic stroke in the hippocampus induced by bilateral injection of endothelin-1 (ET-1). All experimental groups were then tested in the ziggurat task, a new task for spatial cognition. The stress. +. stroke group showed significant deficits in both hippocampal structure and function. No deleterious effect of pre-stroke exposure to CORT was found in the CORT. +. stroke group. Our results indicate that a history of chronic stress sensitizes hippocampal cells to the damaging consequences of focal ischemia. The opposing effects of CORT-related experiences in this study not only reflect the diversity of glucocorticoid actions in the stress response, but also provide evidence that elevated CORT in the absence of emotional disturbance is not sufficient to produce hippocampal deficit. © 2011 Elsevier Inc

Rats with hippocampal lesion show impaired learning and memory in the ziggurat task: A new task to evaluate spatial behavior

Spatial tasks are widely used to determine the function of limbic system structures in rats. The present study used a new task designed to evaluate spatial behavior, the ziggurat task (ZT), to examine the performance of rats with widespread hippocampal damage induced by N-methyl-d-aspartic acid (NMDA). The task consisted of an open field containing 16 identical ziggurats (pyramid shaped towers) arranged at equal distances. One of the ziggurats was baited with a food reward. The task required rats to navigate through the open field by using a combination of distal and/or proximal cues in order to locate the food reward. The ability to acquire and recall the location of the goal (baited) ziggurat was tested in consecutive training sessions of eight trials per day for 10 days. The location of the goal ziggurat was changed every second day, requiring the rats to learn a total of five different locations. Several parameters, including latency to find the target, distance traveled, the number of visits to non-baited ziggurats (errors), and the number of returns were used as indices of learning and memory. Control rats showed a significant decrease in distance traveled and reduced latency in locating the goal ziggurat across trials and days, suggesting that they learned and remembered the location of the goal ziggurat. Interestingly, the hippocampal-damaged group moved significantly faster, and traveled longer distances compared to the control group. Significant differences were observed between these groups with respect to the number of errors and returns on test days. Day 11 served as probe day, in which no food reward was given. The controls spent more time searching for the food in the previous training quadrant compared to the hippocampal group. The findings demonstrate that the ZT is a sensitive and efficient dry task for measuring hippocampus-dependent spatial performance in rats requiring little training and not associated with some of the disadvantages of water tasks. © 2007 Elsevier B.V. All rights reserved

Interplay of Orbital Degeneracy and Superconductivity in a Molecular Conductor

We study electron propagation in a molecular lattice model. Each molecular site involves doubly degenerate electronic states coupled to doubly degenerate molecular vibration, leading to a so--called E-e type of Jahn-Teller Hamiltonian. For weak electron-phonon coupling and in the anti-adiabatic limit we find that the orbital degeneracy induces an intersite pairing mechanism which is absent in the standard non-degenerate polaronic model. In this limit we analyse the model in the presence of an additional on-site repulsion and we determine, within BCS mean field theory, the region of stability of superconductivity. In one dimension, where powerful analytical techniques are available, we are able to calculate the phase diagram of the model both for weak and for strong electron-phonon coupling.Comment: 11 pages, REVTEX style, 3 compressed figures adde

Curricular orientations to real-world contexts in mathematics

A common claim about mathematics education is that it should equip students to use mathematics in the ‘real world’. In this paper, we examine how relationships between mathematics education and the real world are materialised in the curriculum across a sample of eleven jurisdictions. In particular, we address the orientation of the curriculum towards application of mathematics, the ways that real-world contexts are positioned within the curriculum content, the ways in which different groups of students are expected to engage with real-world contexts, and the extent to which high-stakes assessments include real-world problem solving. The analysis reveals variation across jurisdictions and some lack of coherence between official orientations towards use of mathematics in the real world and the ways that this is materialised in the organisation of the content for students

A Green's function approach to transmission of massless Dirac fermions in graphene through an array of random scatterers

We consider the transmission of massless Dirac fermions through an array of short range scatterers which are modeled as randomly positioned $\delta$- function like potentials along the x-axis. We particularly discuss the interplay between disorder-induced localization that is the hallmark of a non-relativistic system and two important properties of such massless Dirac fermions, namely, complete transmission at normal incidence and periodic dependence of transmission coefficient on the strength of the barrier that leads to a periodic resonant transmission. This leads to two different types of conductance behavior as a function of the system size at the resonant and the off-resonance strengths of the delta function potential. We explain this behavior of the conductance in terms of the transmission through a pair of such barriers using a Green's function based approach. The method helps to understand such disordered transport in terms of well known optical phenomena such as Fabry Perot resonances.Comment: 22 double spaced single column pages. 15 .eps figure

Twisted carotenoids do not support efficient intramolecular singlet fission in the orange carotenoid protein

Singlet exciton fission is the spin-allowed generation of two triplet electronic excited states from a singlet state. Intramolecular singlet fission has been suggested to occur on individual carotenoid molecules within protein complexes provided that the conjugated backbone is twisted out of plane. However, this hypothesis has been forwarded only in protein complexes containing multiple carotenoids and bacteriochlorophylls in close contact. To test the hypothesis on twisted carotenoids in a “minimal” one-carotenoid system, we study the orange carotenoid protein (OCP). OCP exists in two forms: in its orange form (OCPo), the single bound carotenoid is twisted, whereas in its red form (OCPr), the carotenoid is planar. To enable room-temperature spectroscopy on canthaxanthin-binding OCPo and OCPr without laser-induced photoconversion, we trap them in a trehalose glass. Using transient absorption spectroscopy, we show that there is no evidence of long-lived triplet generation through intramolecular singlet fission despite the canthaxanthin twist in OCPo

Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Generalized biomolecular modeling and design with RoseTTAFold All-Atom

Deep learning methods have revolutionized protein structure prediction and design but are currently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA) which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies containing proteins, nucleic acids, small molecules, metals, and covalent modifications given their sequences and chemical structures. By fine tuning on denoising tasks we obtain RFdiffusionAA, which builds protein structures around small molecules. Starting from random distributions of amino acid residues surrounding target small molecules, we design and experimentally validate, through crystallography and binding measurements, proteins that bind the cardiac disease therapeutic digoxigenin, the enzymatic cofactor heme, and the light harvesting molecule bilin