Intra-hippocampal administration of the VEGF receptor blocker PTK787/ZK222584 impairs long-term memory.

A number of studies have established a role for vascular endothelial growth factor (VEGF) in angiogenesis. Recent reports have shown that VEGF overexpression in the hippocampus improves learning and memory and is associated with enhanced neurogenesis. PTK787/ZK222584 (PTK/ZK) is a reported inhibitor of VEGFR signaling that is currently being tested for its effects on lung and colon cancer. However, the influence of this drug on cognition has not been examined. In the present study, we questioned if post-training administration of PTK/ZK influences hippocampus-dependent memory. When administered to rats immediately following massed training in the Morris water maze, PTK/ZK impaired spatial memory retention tested 48 h later. This impairment was evidenced by increased latency to the hidden platform and fewer platform crossings. However, this impairment was not associated with a change in neurogenesis during this time frame. PTK/ZK infusion did not reduce VEGFR or AKT phosphorylation, but increased the phosphorylation of ERK. These studies suggest that VEGFR inhibitors such as PTK/ZK may negatively influence cognition

Sulforaphane improves cognitive function administered following traumatic brain injury.

Recent studies have shown that sulforaphane, a naturally occurring compound that is found in cruciferous vegetables, offers cellular protection in several models of brain injury. When administered following traumatic brain injury (TBI), sulforaphane has been demonstrated to attenuate blood-brain barrier permeability and reduce cerebral edema. These beneficial effects of sulforaphane have been shown to involve induction of a group of cytoprotective, Nrf2-driven genes, whose protein products include free radical scavenging and detoxifying enzymes. However, the influence of sulforaphane on post-injury cognitive deficits has not been examined. In this study, we examined if sulforaphane, when administered following cortical impact injury, can improve the performance of rats tested in hippocampal- and prefrontal cortex-dependent tasks. Our results indicate that sulforaphane treatment improves performance in the Morris water maze task (as indicated by decreased latencies during learning and platform localization during a probe trial) and reduces working memory dysfunction (tested using the delayed match-to-place task). These behavioral improvements were only observed when the treatment was initiated 1h, but not 6h, post-injury. These studies support the use of sulforaphane in the treatment of TBI, and extend the previously observed protective effects to include enhanced cognition

The diffusion of IP telephony and vendors' commercialisation strategies

This is a post-peer-review, pre-copyedit version of an article published in the Journal of Information Technology. The definitive publisher-authenticated version is available at the link below.The Internet telephony (IP telephony) has been presented as a technology that can replace existing fixed-line services and disrupt the telecommunications industry by offering new low-priced services. This study investigates the diffusion of IP telephony in Denmark by focusing on vendors’ commercialisation strategies. The theory of disruptive innovation is introduced to investigate vendors’ perceptions about IP telephony and explore their strategies that affect the diffusion process in the residential market. The analysis is based on interview data collected from the key market players. The study's findings suggest that IP telephony is treated as a sustaining innovation that goes beyond the typical voice transmission and enables provision of advanced services such as video telephony

Ants as ecological indicators of rainforest restoration: community convergence and the development of an Ant Forest Indicator Index in the Australian wet tropics

Ecosystem restoration can help reverse biodiversity loss, but whether faunal communities of forests undergoing restoration converge with those of primary forest over time remains contentious. There is a need to develop faunal indicators of restoration success that more comprehensively reflect changes in biodiversity and ecosystem function. Ants are an ecologically dominant faunal group and are widely advocated as ecological indicators. We examine ant species and functional group responses on a chronosequence of rainforest restoration in northern Australia, and develop a novel method for selecting and using indicator species. Four sampling techniques were used to survey ants at 48 sites, from grassland, through various ages (1–24 years) of restoration plantings, to mature forest. From principal components analysis of seven vegetation metrics, we derived a Forest Development Index (FDI) of vegetation change along the chronosequence. A novel Ant Forest Indicator Index (AFII), based on the occurrences of ten key indicator species associated with either grassland or mature forest, was used to assess ant community change with forest restoration. Grasslands and mature forests supported compositionally distinct ant communities at both species and functional levels. The AFII was strongly correlated with forest development (FDI). At forest restoration sites older than 5–10 years that had a relatively closed canopy, ant communities converged on those of mature rainforest, indicating a promising restoration trajectory for fauna as well as plants. Our findings reinforce the utility of ants as ecological indicators and emphasize the importance of restoration methods that achieve rapid closed‐canopy conditions. The novel AFII assessed restoration status from diverse and patchily distributed species, closely tracking ant community succession using comprehensive species‐level data. It has wide applicability for assessing forest restoration in a way that is relatively independent of sampling methodology and intensity, and without a need for new comparative data from reference sites

Quantum Melting and Absence of Bose-Einstein Condensation in Two-Dimensional Vortex Matter

We demonstrate that quantum fluctuations suppress Bose-Einstein condensation of quasi-two-dimensional bosons in a rapidly-rotating trap. Our conclusions rest in part on an effective-Lagrangian description of the triangular vortex lattice, and in part on microscopic Bogoliubov equations in the rapid-rotation limit. We obtain analytic expressions for the collective-excitation dispersion, which, in a rotating system, is quadratic rather than linear. Our estimates for the boson filling factor at which the vortex lattice melts at zero temperature due to quantum fluctuations are consistent with recent exact-diagonalization calculations.Comment: 4 pages, 1 figures, version to appear in Phys. Rev. Let

Carbon nanotube-based sensor and method for detection of crack growth in a structure

A sensor has a plurality of carbon nanotube (CNT)-based conductors operatively positioned on a substrate. The conductors are arranged side-by-side, such as in a substantially parallel relationship to one another. At least one pair of spaced-apart electrodes is coupled to opposing ends of the conductors. A portion of each of the conductors spanning between each pair of electrodes comprises a plurality of carbon nanotubes arranged end-to-end and substantially aligned along an axis. Because a direct correlation exists between the resistance of a carbon nanotube and its strain, changes experienced by the portion of the structure to which the sensor is coupled induce a corresponding change in the electrical properties of the conductors, thereby enabling detection of crack growth in the structure

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Genetic networks controlling retinal injury.

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively