Time-reversal symmetry breaking versus superstructure

One of the mysteries of modern condenced-matter physics is the nature of the pseudogap state of the superconducting cuprates. Kaminski et al.1 claimed to have observed signatures of time-reversal symmetry breaking in the pseudogap regime in underdoped Bi2Sr2CaCu2O8+d (Bi2212). Here we argue that the observed dichroism is due to the 5x1 superstructure replica of the electronic bands and therefore cannot be considered as evidence for the spontaneous time-reversal symmetry breaking in cuprates.Comment: 5 pages, pd

Erosion and the sediment conveyor in central Australia

Why are the Neogene sedimentary fills across central Australia generally thin and discontinuous? One long-standing explanation is that sluggish tectonism and intensified aridity have combined to suppress rates of erosion and sediment production yielding a landscape crowded with inherited, preMiocene forms. Quantifying rates of sediment production, residence time and transport is possible with numerous methods, but the recent growth of cosmogenic nuclide (CN) analysis has provided unprecedented quantitative insights to rates of landscape evolution. Measurements of in situ produced cosmogenic 10Be and 26Al integrate rates of surface processes over million-year timescales—the last part of the Neogene in which aridity has strengthened across the continental interior. We present a compilation of ~600 published and unpublished 10Be and 26Al measurements from central Australia with a focus on the Neogene Eyre Basin and its periphery. Outlying and inlying bedrock uplands serve as engines of sediment production via erosion of bedrock. Surrounding the bedrock outcrops are vast sediment conveyors of varying efficiency and tempo: hillslopes, pediments, and alluvial fans are interim storage/burial zones for sediment in transit to the network of low-gradient rivers, dunes, and playas towards base level. Interactions between fluvial and aeolian processes are especially pertinent to sediment flux in the Eyre Basin. Major rivers such as the Cooper and Finke traverse dunefields in their lower reaches where quantities of alluvia are recirculated into dunes and vice versa. Tracking the trajectories of sediment from source-to-sink (including aeolian recirculation) remains a major challenge, but is central to unravelling the sedimentary dynamics of central Australia's Neogene basins. Based on the CN compilation we estimate 1) spatially averaged erosion rates at the scale of a hillslope or river catchment; 2) pointbased erosion rates on bedrock surfaces; 3) residence time of sediment in hillslope regolith and alluvial fans; and 4) cumulative burial history of sediments in transit. Catchment-scale erosion rates (n~100) are consistently low (<10 m/Myr) and include some of the lowest rates ever measured (~0.3 m/Myr); however, a small group of catchments in the Flinders Ras yield higher erosion rates (~30–60 m/Myr). Bedrock hillslopes (n~200) tend to erode even slower (<5 m/Myr), with a subset of Flinders Ras sites again being the exception (~10–30 m/Myr) and suggesting the influence of recent tectonism. Several CN depth-profiles measured on hillslopes and alluvial fans indicate sediment residence times >0.5 Myr, and high-resolution sampling along three hillslopes with differing morphology (linear, convex, and concave) reveals major variations in sediment production and transport rates that hint at the long-term evolution. In the rivers, fluvial sediments show a weak tendency to increase cumulative burial history downstream (1–2 Myr), consistent with the expanding accommodation space for storage and burial. Dune sediments sampled in the Simpson and Tirari dunefields (n~16) contain cumulative burial histories (up to 1.5 Myr) similar to that of the intersecting rivers. This points to an intimate mix of fluvial and aeolian processes in areas approaching base level. Curiously, these sediments occur in the lowest part of the continent and contain the longest histories of cumulative burial, yet do not form part of the thickest sedimentary fills in the Eyre Basin

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p &#60; 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p &#60; 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension

BACKGROUND: Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling. METHODS AND RESULTS: Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO(2 )= 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-β, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media. CONCLUSION: Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ

Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR) environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants). We measured walking kinematics (joint-angles, velocity profiles) and motor performance (end-point-compensation, trajectory-deviations). Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS) uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation

The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict

Strength of the Spin-Fluctuation-Mediated Pairing Interaction in a High-Temperature Superconductor

Theories based on the coupling between spin fluctuations and fermionic quasiparticles are among the leading contenders to explain the origin of high-temperature superconductivity, but estimates of the strength of this interaction differ widely. Here we analyze the charge- and spin-excitation spectra determined by angle-resolved photoemission and inelastic neutron scattering, respectively, on the same crystals of the high-temperature superconductor YBa2Cu3O6.6. We show that a self-consistent description of both spectra can be obtained by adjusting a single parameter, the spin-fermion coupling constant. In particular, we find a quantitative link between two spectral features that have been established as universal for the cuprates, namely high-energy spin excitations and "kinks" in the fermionic band dispersions along the nodal direction. The superconducting transition temperature computed with this coupling constant exceeds 150 K, demonstrating that spin fluctuations have sufficient strength to mediate high-temperature superconductivity.Comment: 25 pages, 7 figures, including supplementary information, accepted for publication in Nature Physic

Locating Pleistocene Refugia: Comparing Phylogeographic and Ecological Niche Model Predictions

Ecological niche models (ENMs) provide a means of characterizing the spatial distribution of suitable conditions for species, and have recently been applied to the challenge of locating potential distributional areas at the Last Glacial Maximum (LGM) when unfavorable climate conditions led to range contractions and fragmentation. Here, we compare and contrast ENM-based reconstructions of LGM refugial locations with those resulting from the more traditional molecular genetic and phylogeographic predictions. We examined 20 North American terrestrial vertebrate species from different regions and with different range sizes for which refugia have been identified based on phylogeographic analyses, using ENM tools to make parallel predictions. We then assessed the correspondence between the two approaches based on spatial overlap and areal extent of the predicted refugia. In 14 of the 20 species, the predictions from ENM and predictions based on phylogeographic studies were significantly spatially correlated, suggesting that the two approaches to development of refugial maps are converging on a similar result. Our results confirm that ENM scenario exploration can provide a useful complement to molecular studies, offering a less subjective, spatially explicit hypothesis of past geographic patterns of distribution