Examining affective structure in chickens: valence, intensity, persistence and generalization measured using a conditioned place preference test

When measuring animals’ valenced behavioural responses to stimuli, the Conditioned Place Preference (CPP) test goes a step further than many approach-based and avoidance-based tests by establishing whether a learned preference for, or aversion to, the location in which the stimulus was encountered can be generated. We designed a novel, four-chambered CPP test to extend the capability of the usual CPP paradigm to provide information on four key features of animals’ affective responses: valence, scale, persistence and generalization. Using this test, we investigated the affective responses of domestic chickens (Gallus gallus domesticus) to four potentially aversive stimuli: 1. Puffs of air; 2. Sight of (robotic) snake; 3. Sprays of water; 4. Sound of conspecific alarm calls. We found conditioned avoidance of locations associated with the air puffs and water sprays (Friedman’s χ2(3) = 13.323 p > .005; χ2(3) = 14.235 p > .005), but not with the snake and alarm calls. The scale of the learned avoidance was similar for the air puff and water spray stimuli, but persistence and generalization differed. We conclude that the four chambered CPP test can have a valuable role to play in making multi-feature measurements of stimulus-generated affective responses, and we highlight the value of such measurements for improving our understanding of the structure of affect in chickens and other animals

Fabrication & characterisation of Yb³⁺:Er³⁺ phosphosilicate fibres for lasers

Fabrication process of efficient Yb codoped fiber. We explain how we evaluate the fibers and discuss the effect of the ytterbium to erbium concentration ratio on the laser characteristics. Finally, we present results of some investigations into the mechanisms which can affect the efficiency of the lasers, and show that the detrimental up-conversion from the metastable level of the erbium ions is dramatically reduced by the presence of the ytterbium ions

Cross-species genomic and functional analyses identify a combination therapy using a CHK1 inhibitor and a ribonucleotide reductase inhibitor to treat triple-negative breast cancer

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is diagnosed in approximately 15% of all human breast cancer (BrCa) patients. Currently, no targeted therapies exist for this subtype of BrCa and prognosis remains poor. Our laboratory has previously identified a proliferation/DNA repair/cell cycle gene signature (Tag signature) that is characteristic of human TNBC. We hypothesize that targeting the dysregulated biological networks in the Tag gene signature will lead to the identification of improved combination therapies for TNBC. METHODS: Cross-species genomic analysis was used to identify human breast cancer cell lines that express the Tag signature. Knock-down of the up-regulated genes in the Tag signature by siRNA identified several genes that are critical for TNBC cell growth. Small molecule inhibitors to two of these genes were analyzed, alone and in combination, for their effects on cell proliferation, cell cycle, and apoptosis in vitro and tumor growth in vivo. Synergy between the two drugs was analyzed by the Chou-Talalay method. RESULTS: A custom siRNA screen was used to identify targets within the Tag signature that are critical for growth of TNBC cells. Ribonucleotide reductase 1 and 2 (RRM1 and 2) and checkpoint kinase 1 (CHK1) were found to be critical targets for TNBC cell survival. Combination therapy, to simultaneously attenuate cell cycle checkpoint control through inhibition of CHK1 while inducing DNA damage with gemcitabine, improved therapeutic efficacy in vitro and in xenograft models of TNBC. CONCLUSIONS: This combination therapy may have translational value for patients with TNBC and improve therapeutic response for this aggressive form of breast cancer

Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

High-power chirped-pulse all-fiber amplification system based on large-mode-area fiber gratings

The fabrication of large mode-area single mode fibres are crucial to developing high power all-fibre lasers and amplifiers. We report the amplification of picosecond pulses to microjoule energy levels and pulse peak powers in excess of 500kW in an all fiber Chirped Pulse Amplification (CPA) system based on novel large mode area fiber components

Taking stock of gene therapy for cystic fibrosis

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy

RNAi technology and its use in studying the function of nuclear receptors and coregulators

Until just a few years ago, RNA interference (RNAi) technology was restricted to the research fields of plants, C. elegans or Drosophila. The discovery of gene silencing by in vitro synthesized double-stranded RNA (dsRNA) in mammalian cells has made the use of RNAi possible in nearly the entire life science kingdom. DNA vectors delivering small interfering RNA (siRNA) directed by polymerase III or polymerase II promoters to persistently inhibit target genes expression have extended this technology to study in vivo function of these genes. Recently, RNAi has been used as a powerful tool in the functional analysis of nuclear receptors and their coregulators. This short review will cover studies in this area

Long-pulse coherent waveforms from a fiber laser

Passively modelocked long-pulse lasers were made using fiber gratings, MQW nonlinear reflectors and active fiber media. Singlemode Nd- and Er-doped fibers and cladding-pumped fiber lasers operated in high-stability and multi-pulsing regimes

Time-delayed model of RNA interference

RNA interference (RNAi) is a fundamental cellular process that inhibits gene expression through cleavage and destruction of target mRNA. It is responsible for a number of important intracellular functions, from being the first line of immune defence against pathogens to regulating development and morphogenesis. In this paper we consider a mathematical model of RNAi with particular emphasis on time delays associated with two aspects of primed amplification: binding of siRNA to aberrant RNA, and binding of siRNA to mRNA, both of which result in the expanded production of dsRNA responsible for RNA silencing. Analytical and numerical stability analyses are performed to identify regions of stability of different steady states and to determine conditions on parameters that lead to instability. Our results suggest that while the original model without time delays exhibits a bi-stability due to the presence of a hysteresis loop, under the influence of time delays, one of the two steady states with the high (default) or small (silenced) concentration of mRNA can actually lose its stability via a Hopf bifurcation. This leads to the co-existence of a stable steady state and a stable periodic orbit, which has a profound effect on the dynamics of the system