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Robust Response (robust + response)
Selected AbstractsPostexposure feeding depression: A new toxicity endpoint for use in laboratory studies with Daphnia magnaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002Ruth A. McWilliam Abstract In situ bioassays with daphnids currently employ lethality as an endpoint, and although sublethal responses (reproduction and feeding rate) can be measured in the field, such endpoints pose major practical challenges. Previous studies have indicated that Daphnia magna exposed to toxic substances can exhibit delayed recovery in feeding behavior (postexposure feeding depression). This simple, robust response has the potential to be an ecologically relevant and potentially diagnostic endpoint. This study developed and tested the use of postexposure feeding depression as a toxicity endpoint in the laboratory environment. First, replicate numbers were manipulated to produce statistically reliable results. Second, postexposure feeding depression in D. magna was studied under laboratory conditions, by employing toxic substances with differing modes of action. Although most substances caused feeding inhibition during direct exposure, not all substances produced postexposure feeding depression. However, the use of lethality as a supplementary endpoint provided an alternative measure when no feeding depression was apparent after exposure. In combination, these endpoints offer a potentially more sensitive, ecologically relevant alternative to the use of lethality alone for in situ bioassay studies. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Color responses of the human lateral geniculate nucleus: selective amplification of S-cone signals between the lateral geniculate nucleno and primary visual cortex measured with high-field fMRIEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Kathy T. Mullen Abstract The lateral geniculate nucleus (LGN) is the primary thalamic nucleus that relays visual information from the retina to the primary visual cortex (V1) and has been extensively studied in non-human primates. A key feature of the LGN is the segregation of retinal inputs into different cellular layers characterized by their differential responses to red-green (RG) color (L/M opponent), blue-yellow (BY) color (S-cone opponent) and achromatic (Ach) contrast. In this study we use high-field functional magnetic resonance imaging (4 tesla, 3.6 × 3.6 × 3 mm3) to record simultaneously the responses of the human LGN and V1 to chromatic and Ach contrast to investigate the LGN responses to color, and how these are modified as information transfers between LGN and cortex. We find that the LGN has a robust response to RG color contrast, equal to or greater than the Ach response, but a significantly poorer sensitivity to BY contrast. In V1 at low temporal rates (2 Hz), however, the sensitivity of the BY color pathway is selectively enhanced, rising in relation to the RG and Ach responses. We find that this effect generalizes across different stimulus contrasts and spatial stimuli (1-d and 2-d patterns), but is selective for temporal frequency, as it is not found for stimuli at 8 Hz. While the mechanism of this cortical enhancement of BY color vision and its dynamic component is unknown, its role may be to compensate for a weak BY signal originating from the sparse distribution of neurons in the retina and LGN. [source] Implications of future climate and atmospheric CO2 content for regional biogeochemistry, biogeography and ecosystem services across East AfricaGLOBAL CHANGE BIOLOGY, Issue 2 2010RUTH M. DOHERTY Abstract We model future changes in land biogeochemistry and biogeography across East Africa. East Africa is one of few tropical regions where general circulation model (GCM) future climate projections exhibit a robust response of strong future warming and general annual-mean rainfall increases. Eighteen future climate projections from nine GCMs participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment were used as input to the LPJ dynamic global vegetation model (DGVM), which predicted vegetation patterns and carbon storage in agreement with satellite observations and forest inventory data under the present-day climate. All simulations showed future increases in tropical woody vegetation over the region at the expense of grasslands. Regional increases in net primary productivity (NPP) (18,36%) and total carbon storage (3,13%) by 2080,2099 compared with the present-day were common to all simulations. Despite decreases in soil carbon after 2050, seven out of nine simulations continued to show an annual net land carbon sink in the final decades of the 21st century because vegetation biomass continued to increase. The seasonal cycles of rainfall and soil moisture show future increases in wet season rainfall across the GCMs with generally little change in dry season rainfall. Based on the simulated present-day climate and its future trends, the GCMs can be grouped into four broad categories. Overall, our model results suggest that East Africa, a populous and economically poor region, is likely to experience some ecosystem service benefits through increased precipitation, river runoff and fresh water availability. Resulting enhancements in NPP may lead to improved crop yields in some areas. Our results stand in partial contradiction to other studies that suggest possible negative consequences for agriculture, biodiversity and other ecosystem services caused by temperature increases. [source] Upregulation of HTLV-1 and HTLV-2 expression by HIV-1 in vitroJOURNAL OF MEDICAL VIROLOGY, Issue 3 2008Upal Roy Abstract Co-infections with HIV-1 and the human T leukemia virus types 1 and 2 (HTLV-1, HTLV-2) occur frequently, particularly in large metropolitan areas where injection drug use is a shared mode of transmission. Recent evidence suggests that HIV-HTLV co-infections are associated with upregulated HTLV-1/2 virus expression and disease. An in vitro model of HIV-1 and HTLV-1/2 co-infection was utilized to determine if cell free HIV-1 virions or recombinant HIV-1 Tat protein (200,1,000 ng/ml) upregulated HTLV-1/2 expression and infectivity. Exposure to HIV-1 increased the number of HTLV-1 antigen expressing cells, from 6% at baseline to 12% at 24 hr, and 20% at 120 hr (P,<,0.05) post-exposure. A similar, although less robust response was observed in HTLV-2 infected cells. HIV-1 co-localized almost exclusively with HTLV-1/2 positive cells. Exposure to HIV-1 Tat protein (1,000 ng/ml) increased HTLV-1 p19 expression almost twofold by 48 hr, and cells co-stimulated with 10 nM phorbol myristate acetate (PMA) showed almost a fourfold increase over baseline. It is concluded that HIV-1 augments HTLV-1/2 infectivity in vitro. The findings also suggest a role for the HIV-1 Tat protein and PMA-inducible cellular factors, in HIV-1 induced HTLV-1/2 antigen expression. J. Med. Virol. 80:494,500, 2008. © 2008 Wiley-Liss, Inc. [source] Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor AntagonistsALCOHOLISM, Issue 3 2009Angela C. Scibelli Background:, Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol's stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Methods:, Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. Results:, FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. Conclusions:, These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically prescribed due to enhanced sedative effects, enhanced stimulation may also be a concern. [source] Protocol for clinical neurophysiologic examination of the pelvic floorNEUROUROLOGY AND URODYNAMICS, Issue 6 2001Simon Podnar Abstract Clinical neurophysiologic examination of the pelvic floor is performed worldwide, but there is no consensus on the choice of tests, nor on technical details of individual methods. Standardized methods are, however, necessary to obtain their valid application in different laboratories for the purpose of collection of normative data, comparison of patient data and organization of multi-center studies. It is proposed that in patients with suspected "lower motor neuron" type lesions concentric needle electromyography (CNEMG) is the most informative test to detect pelvic floor denervation/reinnervation, and the external anal sphincter (EAS) muscle is the most appropriate muscle to be examined (either in isolation,when a selective lesion is suspected,or in addition to examination of other muscles). An algorithm consisting of standardized tests including a standardized approach to CNEMG examination of the EAS is presented. The proposed electrophysiologic assessment consists of a computer-assisted analysis of denervation and reinnervation features of the CNEMG signal, a qualitative assessment of reflex and voluntary activation of EAS motor units, and of electrical (or mechanical) elicitation of the bulbocavernosus reflex in those patients in whom manual anogenital stimulation failed to elicit a robust response in the EAS. The proposed protocol could serve as a basis for further studies on validity, sensitivity and specificity of electrophysiologic assessment in patients with different types of "lower motor neuron" involvement of pelvic floor muscles and sacral dysfunction. Neurourol. Urodynam. 20:669,682, 2001. © 2001 Wiley-Liss, Inc. [source] NSOM- and AFM-based nanotechnology elucidates nano-structural and atomic-force features of a Y. pestis V immunogen-containing particle vaccine capable of eliciting robust responsePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2009Gucheng Zeng Abstract It is postulated that unique nanoscale proteomic features of immunogen on vaccine particles may determine immunogen-packing density, stability, specificity, and pH-sensitivity on the vaccine particle surface and thus impact the vaccine-elicited immune responses. To test this presumption, we employed near-filed scanning optical microscopy (NSOM)- and atomic force microscopy (AFM)-based nanotechnology to study nano-structural and single-molecule force bases of Yersinia pestis (Y. pestis) V immunogen fused with protein anchor (V-PA) loaded on gram positive enhancer matrix (GEM) vaccine particles. Surprisingly, the single-molecule sensitive NSOM revealed that ,90% of V-PA immunogen molecules were packed as high-density nanoclusters on GEM particle. AFM-based single-molecule force analyses indicated a highly stable and specific binding between V-PA and GEM at the physiological pH. In contrast, this specific binding was mostly abrogated at the acidic pH equivalent to the biochemical pH in phagolysosomes of antigen-presenting-cells in which immunogen protein is processed for antigen presentation. Intranasal mucosal vaccination of mice with such immunogen loaded on vaccine particles elicited robust antigen-specific immune response. This study indicated that high-density, high-stability, specific, and immunological pH-responsive loading of immunogen nanoclusters on vaccine particles could readily be presented to the immune system for induction of strong antigen-specific immune responses. [source] Basic characterization of 90 kDa heat shock protein genes HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 expressed in Japanese quail (Coturnix japonica)ANIMAL SCIENCE JOURNAL, Issue 4 2010Kohji NAGAHORI ABSTRACT In the current study, we describe four novel members of the 90 kDa heat shock protein (HSP90) family expressed in Japanese quail, Coturnix japonica. The coding regions of the genes, CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1, exhibited more than 94% similarity to their related genes in chicken. The putative proteins encoded by these quail genes contained motifs considered essential for HSP90 gene function. In addition, the predicted proteins were more similar to HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 proteins expressed in vertebrates than they were to other members of the HSP90 family. Exon numbers of CjHSP90AA1 (11), CjHSP90AB1 (12) or CjTRAP1 (18) are the same as the chicken and mammalian orthologs. Furthermore, gene order in the regions surrounding CjHSP90AB1 and CjTRAP1 has been preserved, providing evidence that the genomic regions were orthologous to HSP90-containing regions in the chicken genome. The promoter regions of the genes also contained conserved motifs identified in related genes of chicken. However, the nucleotide sequences of the 5,-flanking region of these genes were highly polymorphic. We also found that CjHSP90AA1 exhibited a robust response to heat shock treatment. Taken together, the data suggest that CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1 encode orthologs of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1, respectively. [source] Negative BOLD responses to epileptic spikesHUMAN BRAIN MAPPING, Issue 6 2006Eliane Kobayashi Abstract Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG-fMRI) during interictal epileptiform discharges can result in positive (activation) and negative (deactivation) changes in the blood oxygenation level-dependent (BOLD) signal. Activation probably reflects increased neuronal activity and energy demand, but deactivation is more difficult to explain. Our objective was to evaluate the occurrence and significance of deactivations related to epileptiform discharges in epilepsy. We reviewed all EEG-fMRI studies from our database, identified those with robust responses (P = 0.01, with ,5 contiguous voxels with a |t| > 3.1, including ,1 voxel at |t| > 5.0), and divided them into three groups: activation (A = 8), deactivation (D = 9), and both responses (AD = 43). We correlated responses with discharge type and location and evaluated their spatial relationship with regions involved in the "default" brain state (Raichle et al. [2001]: Proc Natl Acad Sci 98:676,682]. Deactivations were seen in 52/60 studies (AD+D): 26 related to focal discharges, 12 bilateral, and 14 generalized. Deactivations were usually distant from anatomical areas related to the discharges and more frequently related to polyspike- and spike-and-slow waves than to spikes. The "default" pattern occurred in 10/43 AD studies, often associated with bursts of generalized discharges. In conclusion, deactivations are frequent, mostly with concomitant activation, for focal and generalized discharges. Discharges followed by a slow wave are more likely to result in deactivation, suggesting neuronal inhibition as the underlying phenomenon. Involvement of the "default" areas, related to bursts of generalized discharges, provides evidence of a subclinical effect of the discharges, temporarily suspending normal brain function in the resting state. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Intrinsic properties of human and murine memory B cellsIMMUNOLOGICAL REVIEWS, Issue 1 2006Shannon M. Anderson Summary:, The central question of how the immune system responds in a qualitatively and quantitatively better way upon re-exposure to a pathogen is largely unanswered. Both the increased frequency of antigen-specific memory cells and the intrinsic properties that memory cells acquire after antigen experience could contribute to the faster and more robust responses seen after repeated exposure to antigen. In the case of the memory B-cell response, it has been difficult to discern the individual contributions of these two effects. However, because of recent advances in identifying memory B cells, there is an increasing understanding of the intrinsic properties of these cells. The current insights into the unique properties of memory B cells and the progress that has been made in understanding how these affect secondary responses in both the human and the mouse systems are discussed. In addition, we compare the various advantages and disadvantages inherent in each of these systems, in terms of studying the intrinsic properties of memory B cells, and introduce the details of the system that we have developed using conventional heavy chain transgenic (Tgic) mice, which addresses some of the drawbacks of traditional memory models. [source] Collagen promotes sustained glycoprotein VI signaling in platelets and cell linesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2007M. G. TOMLINSON Summary. Background:,Glycoprotein (GP)VI is the major signaling receptor for collagen on platelets and signals via the associated FcR,-chain, which has an immunoreceptor tyrosine-containing activation motif (ITAM). Objective:,To determine why GPVI,FcR, signals poorly, or not at all, in response to collagen in hematopoietic cell lines, despite robust responses to the GPVI-reactive snake venom toxin convulxin. Methods and results:,Using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay, a sensitive readout for sustained ITAM signaling, we demonstrate collagen-induced GPVI,FcR, signaling in hematopoietic cell lines. This is accompanied by relatively weak but sustained protein tyrosine phosphorylation, in contrast to the stronger but transient response to convulxin. Sustained signaling by collagen is also observed in platelets and is necessary for the maintenance of spreading on collagen. Finally, in cell lines, the inhibitory collagen receptor leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), which is not expressed on platelets but is present on most hematopoietic cells, inhibits GPVI responses to collagen but not convulxin. Conclusion:,The inability of previous studies to readily detect GPVI collagen signaling in cell lines is probably because of the weak but sustained nature of the signal and the presence of the inhibitory collagen receptor LAIR-1. In platelets, we propose that GPVI,FcR, has evolved to transmit sustained signals in order to maintain spreading over several hours, as well as facilitating rapid activation through release of feedback agonists and integrin activation. The establishment of a cell line NFAT assay will facilitate the molecular dissection of GPVI signaling and the identification of GPVI antagonists in drug discovery. [source] Mining for robust transcriptional and metabolic responses to long-term salt stress: a case study on the model legume Lotus japonicusPLANT CELL & ENVIRONMENT, Issue 4 2010DIEGO H. SANCHEZ ABSTRACT Translational genomics, the use of model species to generate knowledge about biological processes and the functions of genes, offers great promise to biotechnologists. Few studies have sought robust responses of model plants to environmental stresses, such as salinity, by altering the stress dosage or by repeating experiments in consecutive years and/or different seasons. We mined our published and unpublished data on legume salt acclimation for robust system features at the ionomic, transcriptomic and metabolomic levels. We analysed data from the model legume Lotus japonicus, obtained through six independent, long-term, non-lethal salt stress experiments which were carried out over two consecutive years. Best possible controlled greenhouse conditions were applied and two main questions asked: how reproducible are results obtained from physiologically meaningful salinity experiments, and what degree of bias may be expected if conclusions are drawn from less well-repeated sampling? A surprisingly large fraction of the transcriptional and metabolic responses to salt stress were not reproducible between experiments. A core set of robust changes was found that was shared between experiments. Many of these robust responses were qualitatively and quantitatively conserved between different accessions of the same species, indicating that the robust responses may be a sound starting point for translational genomics. [source] Cancer vaccines: Where are we going?ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2010Jonathan CEBON Abstract The discovery that the immune system can distinguish molecular targets on cancer cells has led to efforts to develop cancer immunotherapeutics that can improve the recognition and effective elimination of tumor cells. Several types of tumor antigens are recognized by T lymphocytes, which are classified according to patterns of gene expression or protein distribution. Of particular interest is the group of molecules known as cancer-germline or cancer-testis antigens. As the relationship between the immune system and cancer has become clearer, so too have the challenges in designing effective cancer immunotherapeutics: (i) antigens need to be specifically selected based on ideal characteristics, such as tissue distribution that is restricted to tumors; (ii) selected antigens need to be combined with adjuvant agents that enhance their immunogenicity and yield robust responses; (iii) vaccination should be timed to pre-empt the development of regulatory suppressive immune mechanisms; and (iv) if suppressive regulatory mechanisms do arise, specific antagonists may be needed to enhance pro-immune outcomes. These challenges are shaping current and future research in this area. [source] | |||||||||||||