Muscarinic receptor-dependent long term depression in the perirhinal cortex and recognition memory are impaired in the rTg4510 mouse model of tauopathy.

This is the final version of the article. Available from the publisher via the DOI in this record.Neurodegenerative diseases affecting cognitive dysfunction, such as Alzheimer's disease and fronto-temporal dementia, are often associated impairments in the visual recognition memory system. Recent evidence suggests that synaptic plasticity, in particular long term depression (LTD), in the perirhinal cortex (PRh) is a critical cellular mechanism underlying recognition memory. In this study, we have examined novel object recognition and PRh LTD in rTg4510 mice, which transgenically overexpress tauP301L. We found that 8-9 month old rTg4510 mice had significant deficits in long- but not short-term novel object recognition memory. Furthermore, we also established that PRh slices prepared from rTg4510 mice, unlike those prepared from wildtype littermates, could not support a muscarinic acetylcholine receptor-dependent form of LTD, induced by a 5 Hz stimulation protocol. In contrast, bath application of the muscarinic agonist carbachol induced a form of chemical LTD in both WT and rTg4510 slices. Finally, when rTg4510 slices were preincubated with the acetylcholinesterase inhibitor donepezil, the 5 Hz stimulation protocol was capable of inducing significant levels of LTD. These data suggest that dysfunctional cholinergic innervation of the PRh of rTg4510 mice, results in deficits in synaptic LTD which may contribute to aberrant recognition memory in this rodent model of tauopathy.SES was supported by a Medical Research Council studentship. JTB was an Alzheimer’s Research UK Senior Research Fellow. Eli Lilly & Co supplied the rTg4510 mice

Reconfigurable architecture for network flow analysis

Abstract—This paper describes a reconfigurable architecture based on field-programmable gate-array (FPGA) technology for monitoring and analyzing network traffic at increasingly high network data rates. Our approach maps the performance-critical tasks of packet classification and flow monitoring into reconfigurable hardware, such that multiple flows can be processed in parallel. We explore the scalability of our system, showing that it can support flows at multi-gigabit rate; this is faster than most software-based solutions where acceptable data rates are typically no more than 100 million bits per second. Index Terms—Flow analysis, flow measurement, network monitor, NetFlow, network security. I

In vitro study of the interaction between some fluoroquinolones and extracts of kola nitida seed

The cup diffusion method (CD) was used to evaluate the in vitro interaction of some fluoroquinolones (ciprofloxacin, pefloxacin and levofloxacin) with extracts of Kola nitida seed (KNS) against a clinical isolate of Escherichia coli. Minimum inhibitory concentration (MIC) of the drugs was determinedseparately and in combination with KNS extract in ratios of 0:5, 1:4, 2:3, 3:2, 4:1 and 5:0 against E. coli. The result of the study revealed that the MIC of the drugs decreased when combined with KNS extract. In other words, KNS extract potentiated the effects of the fluoroquinolones against E. coli

Fuelling expectations: a policy-promise lock-in of UK biofuel policy

Controversy over EU-wide biofuel policy resonated within the UK, fuelling policy disagreements among UK public authorities. They disagreed over how to protect a space for future second-generation biofuels, which were expected to overcome harm from first-generation biofuels. The UK government defended rising targets for available biofuels as a necessary stimulus for industry to help fulfil the UK’s EU obligations and eventually develop second-generation biofuels. By contrast, Parliamentary Select Committees opposed biofuel targets on grounds that these would instead lock-in first-generation biofuels, thus delaying or pre-empting second-generation biofuels. Those disagreements can be explained by different institutional responsibilities and reputational stakes towards ‘promise-requirement cycles’, whereby techno-optimistic promises generate future requirements for the actors involved. The UK government’s stance illustrates a ‘policy-promise lock-in’, a dilemma whereby promised support is a requirement for credibility towards technology innovators and thus technoscientific development – but may delay the redirection of support from incumbent to preferable emerging technologies. Thus the sociology of expectations – previously applied to technological expectations from technology innovators – can be extended to analyse public authorities

A study of the in vitro interaction of cotrimoxazole and ampicillin using the checkerboard method

In this study, the in vitro interaction of two standard antibiotics – cotrimoxazole and ampicillin trihydrate were studied by the checkerboard technique, using clinical isolates of P. aeruginosa, Staphylococcus aureus and Salmonella typhi. The organisms were exposed to the individual antibiotics as well as different combination ratios of the same, and the zones of inhibition as well as the minimum inhibitory concentrations (MICs) measured. Synergistic interactions were recorded by the antibiotics against Staph. aureus and S. typhi while indifferent interaction occurred with P. aeruginosa. P. aeruginosa however, showed resistance to the two antibiotics when they were used alone. The implication is that cotrimoxazole and ampicillin can be used in combination as a superior treatment of infections caused by Staph. aureus and S. typhi

Enhancement of low-energy electron emission in 2D radioactive films

High-energy radiation has been used for decades; however, the role of low-energy electrons created during irradiation has only recently begun to be appreciated. Low-energy electrons are the most important component of radiation damage in biological environments because they have subcellular ranges, interact destructively with chemical bonds, and are the most abundant product of ionizing particles in tissue. However, methods for generating them locally without external stimulation do not exist. Here, we synthesize one-atom-thick films of the radioactive isotope (125)I on gold that are stable under ambient conditions. Scanning tunnelling microscopy, supported by electronic structure simulations, allows us to directly observe nuclear transmutation of individual (125)I atoms into (125)Te, and explain the surprising stability of the 2D film as it underwent radioactive decay. The metal interface geometry induces a 600% amplification of low-energy electron emission (<10 eV; ref. ) compared with atomic (125)I. This enhancement of biologically active low-energy electrons might offer a new direction for highly targeted nanoparticle therapies

Industrial constructions of publics and public knowledge: a qualitative investigation of practice in the UK chemicals industry

This is a post print version of the article. The official published version can be obtained from the link below - © 2007 by SAGE PublicationsWhile the rhetoric of public engagement is increasingly commonplace within industry, there has been little research that examines how lay knowledge is conceptualized and whether it is really used within companies. Using the chemicals sector as an example, this paper explores how companies conceive of publics and "public knowledge," and how this relates to modes of engagement/communication with them. Drawing on qualitative empirical research in four companies, we demonstrate that the public for industry are primarily conceived as "consumers" and "neighbours," having concerns that should be allayed rather than as groups with knowledge meriting engagement. We conclude by highlighting the dissonance between current advocacy of engagement and the discourses and practices prevalent within industry, and highlight the need for more realistic strategies for industry/public engagement.Funding was received from the ESRC Science in Society Programme

Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression

A decision support system for water quality issues in the Manzanares River (Madrid, Spain)

The Manzanares River, located in Madrid (Spain), is the main water supplier of a highly populated region, and it also receives wastewater from the same area. The effluents of eight Waste Water Treatment Plants (WWTPs) downstream of the river, which represent 90% of the flow in the middle and lower parts of the river, are the primary sources of water pollution. Although the situation has improved slightly in the last two years, the water in the river is highly polluted, making it uninhabitable for aquatic life. Water quality modelling is typically used to assess the effect of treatment improvements in water bodies. In this work, the GESCAL module of the Aquatool Decision Support System Shell was used to simulate water quality in the Manzanares River. GESCAL is appropriate for modelling in an integrated way water quality for whole water resources systems, including reservoirs and rivers. A model was built that simulates conductivity, phosphorous, carbonaceous organic matter, dissolved oxygen, organic nitrogen, ammonia, and nitrates. The period from October 2006 to September 2008 was selected for calibration due to the many treatment modifications that occurred during this time. An earlier and longer period, from October 2000 to September 2006, was used for validation. In addition, a daily model was used to analyse the robustness of the GESCAL model. Once the GESCAL model was validated, different scenarios were considered and simulated. First, different combinations of nutrient elimination among the different WWTPs were simulated, leading to the conclusion that investments have to focus on three of the proposed WWTPs. Moreover, these treatments will not be sufficient to maintain fish habitat conditions at all times. Additional measures, such as the increment of the flow in the river or oxygen injection, were simulated. Incrementing the flow of the Manzanares River has been shown to be an efficient means of increasing water quality, but this implies an increment in the risk of water scarcity situations in the Madrid water supply system. © 2010 Elsevier B.V. All rights reserved.This work has been supported by the Spanish Ministry of Science and Innovation through the project Consolider-Ingenio 2010 CSD2009-00065.Paredes Arquiola, J.; Andreu Álvarez, J.; Solera Solera, A. (2010). A decision support system for water quality issues in the Manzanares River (Madrid, Spain). Science of the Total Environment. 408:2576-2589. https://doi.org/10.1016/j.scitotenv.2010.02.037S2576258940