The in vivo proconvulsant effects of corticotropin releasing hormone in the developing rat are independent of ionotropic glutamate receptor activation.

Corticotropin releasing hormone (CRH) produces age-dependent limbic seizures in the infant rat. Both the phenotype and the neuroanatomic matrix of CRH-induced seizures resemble the seizures induced by the rigid glutamate analogue, kainic acid (KA), and by rapid amygdala kindling. The experiments described in this study tested the hypothesis that the in vivo proconvulsant effects of CRH require activation of ionotropic glutamate receptors. Non-competitive (+MK-801) or competitive (CGP-39551) antagonists of N-methyl-d-aspartate (NMDA) receptors decreased or eliminated the motor effects of CRH, but electrographic CRH-induced seizures were unaffected. Administration of CRH antagonists did not affect the acquisition or the maintenance of rapid kindling, which are mediated by NMDA and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor activation, respectively. CRH receptor blockers failed to alter the latency or duration of seizures induced by activation of KA receptors, and threshold doses of CRH and KA had additive effects. CRH given repeatedly decreased the convulsant threshold dose of KA, probably via injury to hippocampal neurons. These results suggest that CRH and glutamate increase neuronal excitability via independent mechanisms. Because the proconvulsant effects of CRH are highly specific to the developmental period, glutamate-receptor-independent, CRH-receptor mediated excitation may account for some of the enhanced susceptibility to seizures during this period

Self-similarity of the meddy family in the eastern North Atlantic

In this study we analyze two groups of Mediterranean salt lenses: "mid-life' lenses, typically 1-2 years old, observed in the Canary Basin, and younger Meddies from the Iberian Basin. Nonlinear transformation of variables is used to find a unique function describing vertical profiles at different locations inside the lens. When this function is found, its existence is considered as "self-similarity' of the lens structure. A common function was also found that describes each group of Meddy, Canary and Iberian, and a remarkable difference between the groups was noted. A possible reason for this result might lie in the difference in lens age. -from Author

Critical exponents of a multicomponent anisotropic t-J model in one dimension

A recently presented anisotropic generalization of the multicomponent supersymmetric $t-J$ model in one dimension is investigated. This model of fermions with general spin-$S$ is solved by Bethe ansatz for the ground state and the low-lying excitations. Due to the anisotropy of the interaction the model possesses $2S$ massive modes and one single gapless excitation. The physical properties indicate the existence of Cooper-type multiplets of $2S+1$ fermions with finite binding energy. The critical behaviour is described by a $c=1$ conformal field theory with continuously varying exponents depending on the particle density. There are two distinct regimes of the phase diagram with dominating density-density and multiplet-multiplet correlations, respectively. The effective mass of the charge carriers is calculated. In comparison to the limit of isotropic interactions the mass is strongly enhanced in general.Comment: 10 pages, 3 Postscript figures appended as uuencoded compressed tar-file to appear in Z. Phys. B, preprint Cologne-94-474

Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Brain computer tomography in critically ill patients -- a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients.</p> <p>Methods</p> <p>In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An “expected abnormality” was any finding that had been predicted by the physician requesting the brain CT. A brain CT was “diagnostically positive”, if the abnormality found was new or if an already known abnormality was increased. It was “diagnostically negative” if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as “treatment as planned”, “treatment changed, not as planned”, “treatment unchanged”.</p> <p>Results</p> <p>Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), <it>p</it> 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned.</p> <p>Conclusions</p> <p>The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.</p

Influence of soil water content and atmospheric conditions on leaf water potential in cv. "Touriga Nacional" deep-rooted vineyards

Abstract In this study, the influence of soil and atmosphere conditions on noon and basal leaf water potential of vines ‘‘Touriga Nacional’’ in the Da˜o region submitted to different irrigation treatments is analysed. Both indicators showed to be dependent on environmental conditions at the time of measurement. Leaf water potential at noon of fully watered plants was linearly related with atmospheric conditions, with values registered when vapour pressure deficit (VPD) was higher than approximately 3 kPa being no different from the values registered in stressed plants. Therefore, this indicator cannot be reliably used to distinguish different plant water stress levels when atmospheric conditions induce high evaporative demands. The basal leaf water potential (wb) was also influenced by VPD at the time of measurement for all soil water conditions. In well irrigated plants, it was even possible to establish a baseline that can therefore be used to identify nonwater stressed conditions (wb (MPa) = -0.062–0.0972 VPD (kPa), r2 = 0.78). A good correlation was found between soil humidity and wb. However, more than the average value of the whole thickness of soil monitored, the wb values were dependent on the distribution of soil humidity, with the plants responding to the presence of wet layers

Global Analysis of Proline-Rich Tandem Repeat Proteins Reveals Broad Phylogenetic Diversity in Plant Secretomes

Cell walls, constructed by precisely choreographed changes in the plant secretome, play critical roles in plant cell physiology and development. Along with structural polysaccharides, secreted proline-rich Tandem Repeat Proteins (TRPs) are important for cell wall function, yet the evolutionary diversity of these structural TRPs remains virtually unexplored. Using a systems-level computational approach to analyze taxonomically diverse plant sequence data, we identified 31 distinct Pro-rich TRP classes targeted for secretion. This analysis expands upon the known phylogenetic diversity of extensins, the most widely studied class of wall structural proteins, and demonstrates that extensins evolved before plant vascularization. Our results also show that most Pro-rich TRP classes have unexpectedly restricted evolutionary distributions, revealing considerable differences in plant secretome signatures that define unexplored diversity