Tourette syndrome research highlights 2015 [version 1; referees: 3 approved]

We present selected highlights from research that appeared during 2015 on Tourette syndrome and other tic disorders. Topics include phenomenology, comorbidities, developmental course, genetics, animal models, neuroimaging, electrophysiology, pharmacology, and treatment. We briefly summarize articles whose results we believe may lead to new treatments, additional research or modifications in current models of TS

Insect expression systems : improving intracellular and heterologous gene expression

Expression systems (ES) in a wide variety of biological systems are used to provide foreign protein. Protein production in mammalian cells is a labour-intensive and expensive process and insect cells have been used as cheaper alternatives. Insect ES are based on two types of vector; viral- and plasmid-based. The baculovirus ES (BES) offers high-level transient production of intracellular proteins. Yields of secreted and membrane-targeted proteins have until recently been relatively low, however, the development of a novel vector, lacking chitinase, has overcome these limitations. Plasmid-based vectors can be used for transient and stable expression in insect cells but most utilise the relatively weak Autographa californica multiple nucleopolyhedrovirus (AcMNPV) immediate early-1 (ie-1) promoter, producing low-levels of intracellular recombinant protein. More recent vectors have used stronger promoters, however, compared with mammalian stable ES these are limited in use and most notable is the lack of an efficient inducible ES in insect cells. The work in this thesis describes methods, with which intracellular levels of foreign protein may be increased, while also developing the grounding work for the development of a fully functional insect tetracycline regulatory system. To improve stable and regulated expression of heterologous genes in insect cells, work was undertaken to compare and characterise the transcriptional activity of a range of promoters successfully used in insect and mammalian systems. Of the promoters tested, Orgyia pseudotsugata MNPV (Op) ie-2 and Bombyx morl actin 3 (BmA3+E) were found to be transcriptionally stronger than AcMNPV ie-1. Drosophila melanogaster metallothionein and actin 5.1 did not produce any detectable activity, and the Cytomegalovirus (CMV) ie promoter, although active, was weaker than AcMNPV ;e-1. Attempts to develop a new inducible ES for use in stable cell lines was based on modifying a mammalian tetracyclineinducible ES. The original CMVie promoters were replaced by the Bm A3+E and Op ie-2 promoters that had been shown to be optimal in insect cells. The Bm A3+E promoter was successfully used to express the tetracycline transcriptional activator protein. Studies also demonstrated that the constitutive transcriptional activity of Op ie-2, used to drive expression of a reporter gene, was successfully suppressed in normal medium. However, in the presence of the inducer, doxycycline, transcriptional activity of Op ie-2 was not activated. Work to elucidate why Op ie-2 remain repressed in the presence of the inducer, indicated that other, uncharacterised vector sequences may have interfered with the activation process. To determine whether stable insect cell lines could be used as an effective alternative to the BES for producing large quantities of intracellular foreign proteins, protein production from stable cell lines, using the Bm A3+E promoter, were compared to the BES using a range of reporter proteins. It was concluded that with vectors currently available, stable cell lines would not normally provide an effective alternative to the BES. However, a stable insect cell line expressing Discosoma red was used to develop methods for scaling-up continuous cultivation of cells in an open fermenter system. This stable cell line was successfully maintained without contamination or total loss of cell viability for 4 weeks. Improving intracellular expression of foreign genes using the BES, initially focused on investigating whether a baculovirus vector (BV) lacking chitinase could produce larger yields than normal BV. It was concluded that recombinant BV lackingchitinase could be used to improve intracellular levels of foreign protein, but demonstrated the importance of optimiSing production conditions for each recombinant protein (e.g., vector and cell line). Intracellular levels of foreign protein were further improved from the BES using different culturing methodologies (fermentation and shaker flask) and concluded that fermenters produced optimal conditions for intracellular protein production, probably due to maintaining a constant level of dissolved oxygen concentration during virus infection

Effect of Agricultural Practices on Nitrate Leaching

Teagasc wishes to acknowledge with gratitude funding from the 2000-2006 EPA RTDI programme in financing this research project.End of project reportA farm-scale study, carried out at Teagasc, Moorepark (Curtin’s farm), examined the effect of four managements (treatments) on nitrate-nitrogen (NO3-N) leaching over the period 2001-`05. Leaching was measured in these treatments: (T1) plots receiving dirty water and N fertilizer which were grazed; (T2) 2-cut silage and grazing plots receiving slurry and fertilizer N; (T3) grazed plots receiving fertilizer N and (T4) 1-cut silage and grazing plots receiving slurry and fertilizer N. The soil is a free-draining sandy loam overlying Karstic fissured limestone. The mean direct N inputs (kg/ha) for T1-T4 in 2001-`04 were 311, 309, 326, 331, respectively, with stocking rates (LU/ha) of 2.12 - ~2.47. Eight ceramic cups per plot, in 3 replicate plots of each treatment, were used to collect water, on a weekly basis, from 1.0 m deep using 50 kPa suction. There were 33, 37, 26 and 24 sampling dates in the 4 years, respectively. The NO3-N and NH4-N concentrations (mg/l) were determined in the water samples. The annual average and weekly concentration of these parameters was statistically analysed for all years, using a repeated measures analysis. The aggregated data were not normally distributed. There was an interaction between treatment and year (p<0.001). Significant differences (p=0.05) in NO3-N concentrations showed between the treatments in years 1, 2, 4 but not in year 3. For the NH4-N data there was no interaction between treatment and year, p=0.12, or main effect of treatment, p=0.54 but there were differences between years, p=0.01. Mean weekly concentrations were analysed separately for each year. For NO3-N, in years 1, 2 and 4 there was an interaction between treatment and week (p<0.001). With NH4-N, there was an interaction between treatment and week in all 4 years. Dirty water was significantly higher than grazed and 1 cut silage in NO3-N concentrations in year 1; in year 2, dirty water and 2 cut silage were significantly higher than the other treatments while in year 4, dirty water and grazed were significantly higher than the other two treatments. The overall four-year weighted mean NO3-N and NH4-N concentrations were 8.2 and 0.297 mg/l. The NCYCLE (UK) model was adapted for Irish conditions as NCYCLE_IRL. The NCYCLE empirical approach proved to be suitable to predict N fluxes from Irish grassland systems in most situations. Experimental data appeared to agree quite well, in most cases, with the outputs from NCYCLE_IRL. The model was not capable of predicting data from some of the leaching experiments, which suggests that the observed leaching phenomena in these experiments could be governed by non-average conditions or other parameters not accounted for in NCYCLE_IRL. An approach that took into account denitrification, leaching and herbage yield would probably explain the differences found. NCYCLE_IRL proved to be a useful tool to analyse N leaching from grazed and cut grassland systems in Ireland.Environmental Protection Agenc

Tourette Syndrome research highlights 2014

About 200 journal articles reported research on Tourette syndrome and other tic disorders in 2014. Here we briefly summarize a few of the reports that seemed most important or interesting, ranging from animal models to human studies. Readers can comment on our choices or provide their own favorites using the tools on the online article

Obasanjo and the verdict of history: an assessment of Obasanjo’s administration in Nigeria 1999-2007

The history of modern Nigeria cannot be complete without a mention of Chief Olusegun Obasanjo. This is certainly because of the roles he had played in the leadership of Nigeria. He ruled Nigeria as a military Head of State from 1976 to 1979 and as a civilian president from 1999-2007, a feat no other Nigerian had accomplished. The essence of this paper is to ascertain the verdict of history on Obasanjo as a military Head of State and more especially as a civilian president from 1999-2007. His term as a civilian president was a major litmus test for the future of Nigeria’s fledgling democracy. Set as a critical conjecture characterized by high popular expectation and international goodwill on the one hand, and weak institutions and deep seated social cleavages exacerbated by years of military rule on the other, his administration was expected to quickly deliver the dividends of democracy. How far did he go and how positively or negatively had he impacted on Nigerians and the Nigerian nation

The Obscured Fraction of AGN in the XMM-COSMOS Survey: A Spectral Energy Distribution Perspective

The fraction of AGN luminosity obscured by dust and re-emitted in the mid-IR is critical for understanding AGN evolution, unification, and parsec-scale AGN physics. For unobscured (Type-1) AGN, where we have a direct view of the accretion disk, the dust covering factor can be measured by computing the ratio of re-processed mid-IR emission to intrinsic nuclear bolometric luminosity. We use this technique to estimate the obscured AGN fraction as a function of luminosity and redshift for 513 Type-1 AGN from the XMM-COSMOS survey. The re-processed and intrinsic luminosities are computed by fitting the 18-band COSMOS photometry with a custom SED-fitting code, which jointly models emission from: hot-dust in the AGN torus, the accretion disk, and the host-galaxy. We find a relatively shallow decrease of the luminosity ratio as a function of Lbol, which we interpret as a corresponding decrease in the obscured fraction. In the context of the receding torus model, where dust sublimation reduces the covering factor of more luminous AGN, our measurements require a torus height which increases with luminosity as h ~ Lbol^{0.3-0.4}. Our obscured fraction-luminosity relation agrees with determinations from SDSS censuses of Type-1 and Type-2 quasars, and favors a torus optically thin to mid-IR radiation. We find a much weaker dependence of obscured fraction on 2-10 keV luminosity than previous determinations from X-ray surveys, and argue that X-ray surveys miss a significant population of highly obscured Compton-thick AGN. Our analysis shows no clear evidence for evolution of obscured fraction with redshift.Comment: 33 pages, 24 figures, ApJ accepte

Sensory-specific Appetition: Postingestive Detection of Glucose Rapidly Promotes Continued Consumption of a Recently Encountered Flavor

It is generally thought that macronutrients stimulate intake when sensed in the mouth (e.g., sweet taste) but as food enters the GI tract its effects become inhibitory, triggering satiation processes leading to meal termination. Here we report experiments extending recent work (see [1]) showing that under some circumstances nutrients sensed in the gut produce a positive feedback effect, immediately promoting continued intake. In one experiment, rats with intragastric (IG) catheters were accustomed to consuming novel flavors in saccharin daily while receiving water infused IG (5 ml/15 min). The very first time glucose (16% w/w) was infused IG instead of water, intake accelerated within 6 mins of infusion onset and total intake increased 29% over baseline. Experiment 2 replicated this stimulatory effect with glucose infusion but not fructose nor maltodextrin. Experiment 3 showed the immediate intake stimulation is specific to the flavor accompanying the glucose infusion. Rats were accustomed to flavored saccharin being removed and replaced with the same or a different flavor. When glucose infusion accompanied the first bottle, intake from the second bottle was stimulated only when it contained the same flavor, not when the flavor switched. Thus we confirm not only that glucose sensed postingestively can have a rapid, positive feedback effect (\u27appetition\u27 as opposed to \u27satiation\u27) but that it is sensory-specific, promoting continued intake of a recently encountered flavor. This sensory specific motivation may represent an additional psychobiological influence on meal size, and further, has implications for the mechanisms of learned flavor-nutrient associations