An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires

Nanomaterials with enzyme-like properties has attracted significant interest, although limited information is available on their biological activities in cells. Here we show that V2O5 nanowires (Vn) functionally mimic the antioxidant enzyme glutathione peroxidase by using cellular glutathione. Although bulk V2O5 is known to be toxic to the cells, the property is altered when converted into a nanomaterial form. The Vn nanozymes readily internalize into mammalian cells of multiple origin (kidney, neuronal, prostate, cervical) and exhibit robust enzyme-like activity by scavenging the reactive oxygen species when challenged against intrinsic and extrinsic oxidative stress. The Vn nanozymes fully restore the redox balance without perturbing the cellular antioxidant defense, thus providing an important cytoprotection for biomolecules against harmful oxidative damage. Based on our findings, we envision that biocompatible Vn nanowires can provide future therapeutic potential to prevent ageing, cardiac disorders and several neurological conditions, including Parkinson's and Alzheimer's disease.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent. (c) 2011 Wiley Periodicals, Inc.

Multi-species and multi-interest management: An ecosystem approach to market squid (Loligo opalescens) harvest in California

Market squid (Loligo opalescens) plays a vital role in the California ecosystem and serves as a major link in the food chain as both a predator and prey species. For over a century, market squid has also been harvested off the California coast from Monterey to San Pedro. Expanding global markets, coupled with a decline in squid product from other parts of the world, in recent years has fueled rapid expansion of the virtually unregulated California fishery. Lack of regulatory management, in combination with dramatic increases in fishing effort and landings, has raised numerous concerns from the scientific, fishing, and regulatory communities. In an effort to address these concerns, the National Oceanic and Atmospheric Administration’s (NOAA) Channel Islands National Marine Sanctuary (CINMS) hosted a panel discussion at the October 1997 California Cooperative Oceanic and Fisheries Investigations (CalCOFI) Conference; it focused on ecosystem management implications for the burgeoning market squid fishery. Both panel and audience members addressed issues such as: the direct and indirect effects of commercial harvesting upon squid biomass; the effects of harvest and the role of squid in the broader marine community; the effects of environmental variation on squid population dynamics; the sustainability of the fishery from the point of view of both scientists and the fishers themselves; and the conservation management options for what is currently an open access and unregulated fishery. Herein are the key points of the ecosystem management panel discussion in the form of a preface, an executive summary, and transcript. (PDF contains 33 pages.)

Adsorption of formaldehyde molecule on the intrinsic and Al-doped graphene: a first principle study

To search for a high sensitivity sensor for formaldehyde (H2CO), We investigated the adsorption of H2CO on the intrinsic and Al-doped graphene sheets using density functional theory (DFT) calculations. Compared with the intrinsic graphene, the Al-doped graphene system has high binding energy value and short connecting distance, which are caused by the chemisorption of H2CO molecule. Furthermore, the density of states (DOS) results show that orbital hybridization could be seen between H2CO and Al-doped graphene sheet, while there is no evidence for hybridization between the H2CO molecule and the intrinsic graphene sheet. Therefore, Al-doped graphene is expected to be a novel chemical sensor for H2CO gas. We hope our calculations are useful for the application of graphene in chemical sensor.

Evaluation of Speaker Normalization Methods for Vowel Recognition Using Fuzzy ARTMAP and K-NN

A procedure that uses fuzzy ARTMAP and K-Nearest Neighbor (K-NN) categorizers to evaluate intrinsic and extrinsic speaker normalization methods is described. Each classifier is trained on preprocessed, or normalized, vowel tokens from about 30% of the speakers of the Peterson-Barney database, then tested on data from the remaining speakers. Intrinsic normalization methods included one nonscaled, four psychophysical scales (bark, bark with end-correction, mel, ERB), and three log scales, each tested on four different combinations of the fundamental (Fo) and the formants (F1 , F2, F3). For each scale and frequency combination, four extrinsic speaker adaptation schemes were tested: centroid subtraction across all frequencies (CS), centroid subtraction for each frequency (CSi), linear scale (LS), and linear transformation (LT). A total of 32 intrinsic and 128 extrinsic methods were thus compared. Fuzzy ARTMAP and K-NN showed similar trends, with K-NN performing somewhat better and fuzzy ARTMAP requiring about 1/10 as much memory. The optimal intrinsic normalization method was bark scale, or bark with end-correction, using the differences between all frequencies (Diff All). The order of performance for the extrinsic methods was LT, CSi, LS, and CS, with fuzzy AHTMAP performing best using bark scale with Diff All; and K-NN choosing psychophysical measures for all except CSi.

Speaker Normalization Methods for Vowel Cognition: Comparative Analysis Using Neural Network and Nearest Neighbor Classifiers

Intrinsic and extrinsic speaker normalization methods are systematically compared using a neural network (fuzzy ARTMAP) and L1 and L2 K-Nearest Neighbor (K-NN) categorizers trained and tested on disjoint sets of speakers of the Peterson-Barney vowel database. Intrinsic methods include one nonscaled, four psychophysical scales (bark, bark with endcorrection, mel, ERB), and three log scales, each tested on four combinations of F0 , F1, F2, F3. Extrinsic methods include four speaker adaptation schemes, each combined with the 32 intrinsic methods: centroid subtraction across all frequencies (CS), centroid subtraction for each frequency (CSi), linear scale (LS), and linear transformation (LT). ARTMAP and KNN show similar trends, with K-NN performing better, but requiring about ten times as much memory. The optimal intrinsic normalization method is bark scale, or bark with endcorrection, using the differences between all frequencies (Diff All). The order of performance for the extrinsic methods is LT, CSi, LS, and CS, with fuzzy ARTMAP performing best using bark scale with Diff All; and K-NN choosing psychophysical measures for all except CSi.

Simulating Effects of Learning and Lesions with a Model of Intrinsic and Synaptically Gated Responses of Striatal Cholinergic Interneurons

The giant cholinergic interneurons of the striatum are tonically active neurons (TANs) that respond with characteristic pauses to novel events and to appetitive and aversive conditioned stimuli. Fluctuations in acetylcholine release by TANs modulate performance- and learning-related dynamics in the striatum. Whereas tonic activity emerges from intrinsic properties of these neurons, glutamatergic inputs from thalamic centromedian-parafascicular nuclei, and dopaminergic inputs from midbrain, are required for the generation of pause responses. No prior computational models encompass both intrinsic and synaptically-gated dynamics. We present a mathematical model that robustly accounts for behavior-related electrophysiological properties of TANs in terms of their intrinsic physiological properties and known afferents. In the model, balanced intrinsic hyperpolarizing and depolarizing currents engender tonic firing, and glutamatergic inputs from thalamus (and cortex) both directly excite and indirectly inhibit TANs. If the latter inhibition, presumably mediated by GABAergic interneurons, exceeds a threshold, its effect is amplified by a KIR current to generate a prolonged pause. In the model, the intrinsic mechanisms and external inputs are both modulated by learning-dependent dopamine (DA) signals and our simulations revealed that many learning-dependent behaviors of TANs are explicable without recourse to learning-dependent changes in synapses onto TANs. The "teaching signal" that modulates reinforcement learning at cortico-striatal synapses may be a sequence composed of an adaptively scaled DA burst, a brief ACh burst, and a scaled ACh pause. Such an interpretation is consistent with recent data on cholinergic control of LTD of cortical synapses onto striatal spiny projection neurons.

The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running.

Age and gender influences on sensory perceptions of novel low cost nutrient-rich food products developed using traditional Ghanaian food ingredients

Background: A number of factors are known to influence food preferences and acceptability of new products. These include their sensory characteristics and strong, innate neural influences. In designing foods for any target group, it is important to consider intrinsic and extrinsic characteristics which may contribute to palatability, and acceptability of foods. Objective: To assess age and gender influences on sensory perceptions of novel low cost nutrient-rich food products developed using traditional Ghanaian food ingredients. Materials and Methods: In this study, a range of food products were developed from Ghanaian traditional food sources using the Food Multimix (FMM) concept. These products were subjected to sensory evaluation to assess the role of sensory perception on their acceptability among different target age groups across the life cycle (aged 11-68 years olds) and to ascertain any possible influences of gender on preference and choice. Variables including taste, odour, texture, flavour and appearance were tested and the results captured on a Likert scale and scores of likeness and acceptability analysed. Multivariate analyses were used to develop prediction models for targeted recipe development for different target groups. Multiple factor analysis of variance (ANOVA) and logistic linear regression were employed to test the strength of acceptability and to ascertain age and gender influences on product preference. Results: The results showed a positive trend in acceptability (r = 0.602) which tended towards statistical significance (p = 0.065) with very high product favourability rating (91% acceptability; P=0.005). However, age [odds ratios=1.44 (11-15 years old) odds ratios=2.01 (18-68 years old) and gender (P=0.000)] were major influences on product preference with children and females (irrespective of age) showing clear preferences or dislike of products containing certain particular ingredients. Conclusion: These findings are potentially useful in planning recipes for feeding interventions involving different vulnerable and target groups.