Preliminary results from a simulation of quenched QCD with overlap fermions on a large lattice

We simulate quenched QCD with the overlap Dirac operator. We work with the Wilson gauge action at beta=6 on an 18^3x64 lattice. We calculate quark propagators for a single source point and quark mass ranging from am_q=0.03 to 0.75. We present here preliminary results based on the propagators for 60 gauge field configurations.Comment: Lattice2003(chiral); 9 latex pages (espcrc2.sty), 13 figures. Based on talks given by C.H., L.L. and C.R. at 21st International Symposium on Lattice Field Theory (Lattice 2003), Tsubuka, Japan, 15-19 July 2003. Repitition in references corrected and one reference adde

Mol Vis

PURPOSE: To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65(-)/(-) mouse model of Leber congenital amaurosis. METHODS: We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5(-)/(-)/Rpe65(-)/(-)). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Transcriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin alpha subunit (Gnat1), and cone transducin alpha subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. RESULTS: No differences in the progression of retinal degeneration were observed between the Rpe65(-)/(-) and Cspg5(-)/(-)/Rpe65(-)/(-) mice. No retinal phenotype was detected in the late postnatal and adult Cspg5(-)/(-) mice, when compared to the wild-type mice. CONCLUSIONS: Despite the previously reported upregulation of Cspg5 during retinal degeneration in Rpe65(-)/(-) mice, no protective effect or any involvement of Cspg5 in disease progression was identified

Stringing Spins and Spinning Strings

We apply recently developed integrable spin chain and dilatation operator techniques in order to compute the planar one-loop anomalous dimensions for certain operators containing a large number of scalar fields in N =4 Super Yang-Mills. The first set of operators, belonging to the SO(6) representations [J,L-2J,J], interpolate smoothly between the BMN case of two impurities (J=2) and the extreme case where the number of impurities equals half the total number of fields (J=L/2). The result for this particular [J,0,J] operator is smaller than the anomalous dimension derived by Frolov and Tseytlin [hep-th/0304255] for a semiclassical string configuration which is the dual of a gauge invariant operator in the same representation. We then identify a second set of operators which also belong to [J,L-2J,J] representations, but which do not have a BMN limit. In this case the anomalous dimension of the [J,0,J] operator does match the Frolov-Tseytlin prediction. We also show that the fluctuation spectra for this [J,0,J] operator is consistent with the string prediction.Comment: 27 pages, 4 figures, LaTex; v2 reference added, typos fixe

A pilot randomised controlled trial using prophylactic dressings to minimise sacral pressure injuries in high risk hospitalised patients

This pilot randomised controlled trial examined the effect of prophylactic dressings to minimise sacral pressure injuries in high-risk hospitalised patients and assessed feasibility criteria to inform a larger study. Eighty patients were recruited at admission points (the Emergency Department and Surgical Care Unit) or directly from participating wards in the general medical surgical setting following assessment of high risk for sacral pressure injury. Participants were randomised into either the routine care or routine care and silicone foam border dressing group. Outcome assessment comprised digital photographs of each participant’s sacrum every 72 hours for evaluation by a blind-to-intervention assessor. Sixty-seven participants had at least one sacral photograph taken and assessed by a blind-to-intervention assessor. Three participants were assessed as having a Stage I pressure injury. While the use of photography was effective, feasibility criteria identified challenges related to bias, blinding, weight assessment, preparation of nursing staff and sample size estimation

The Cyanobacterial Hepatotoxin Microcystin Binds to Proteins and Increases the Fitness of Microcystis under Oxidative Stress Conditions

Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites

The role of the VEGF-C/VEGFR-3 axis in cancer progression

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression

Targeting lymphangiogenesis to prevent tumour metastasis

Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involves the secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3) localised on the surface of lymphatic endothelial cells. In this review, we discuss the evidence supporting a role for this signalling system in the spread of cancer and potential approaches for blocking this system to prevent tumour metastasis

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment