Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Cumulate causes for the low contents of sulfide-loving elements in the continental crust

Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

Dietary intake of professional Australian football athletes surrounding body composition assessment

© 2018 The Author(s). Background: Sports Dietitians aim to assist in improving performance by developing nutrition knowledge (NK), enhancing dietary intake and optimising body composition of athletes. In a high-pressure environment, it is important to identify factors that may compromise an athlete's nutrition status. Body composition assessments are regularly undertaken in sport to provide feedback on training adaptions; however, no research has explored the impact of these assessments on the dietary intake of professional athletes. Methods: This cross-sectional study assessed dietary intake (7-day food diary), nutrition knowledge (Nutrition for Sport Knowledge Questionnaire) and body composition (Dual-energy X-ray absorptiometry) of 46 professional male Australian football (AFL) athletes during a 2017 pre-season training week (7days) where body composition assessments were undertaken. Dietary intake was assessed against International Olympic Committee recommendations for professional athletes. Results: Overall, no athlete met dietary their recommended energy intake (15±1.1 vs. 9.1±1.8MJ, respectively) or carbohydrate recommendations (6-10 vs. 2.4±0.9g.kg-1.day-1). Only 54% met protein recommendations. Secondary analyses demonstrated significant associations between education status and energy intake (P<0.04) and vegetable intake (P<0.03), with higher levels of education being associated with higher intakes. A moderately positive association was observed between NK scores and meeting estimated energy requirements (r=0.33, P=0.03). NK scores were also positively associated with protein (r=0.35, P=0.02), fibre (r=0.51, P=0.001) and calcium intakes (r=0.43, P=0.004). Conclusions: This research identified that the dietary intake of professional AFL athletes during a pre-season training week where body composition assessments were undertaken did not meet current recommendations. Several factors may influence the dietary intake of AFL athletes, including lower education levels, poor NK and dietary intake restriction surrounding body composition assessment. Athletes may require support to continue with performance-based nutrition plans in periods surrounding body composition assessment

Accelerator system for the PRISM based muon to electron conversion experiment

The next generation of lepton flavor violation experiments need high intensity and high quality muon beams. Production of such beams requires sending a short, high intensity proton pulse to the pion production target, capturing pions and collecting the resulting muons in the large acceptance transport system. The substantial increase of beam quality can be obtained by applying the RF phase rotation on the muon beam in the dedicated FFAG ring, which was proposed for the PRISM project.This allows to reduce the momentum spread of the beam and to purify from the unwanted components like pions or secondary protons. A PRISM Task Force is addressing the accelerator and detector issues that need to be solved in order to realize the PRISM experiment. The parameters of the required proton beam, the principles of the PRISM experiment and the baseline FFAG design are introduced. The spectrum of alternative designs for the PRISM FFAG ring are shown. Progress on ring main systems like injection and RF are presented. The current status of the study and its future directions are discussed.Comment: Studies performed within the PRISM Task Force initiativ

Річард Смоллі і знамениті «десять вересневих днів»

У вересні цього року виповнюється 27 років, як було відкрито фулерен — нову сфероподібну форму вуглецю. Ця подія буквально приголомшила вчених, які на той час вважали, що про елементарний вуглець їм відомо практично все. Історія відкриття цієї речовини досить незвичайна. Ще в 1971 р. можливість існування молекули фулерену була передбачена японським ученим Е. Осавою (E. Osawa), за два роки радянські хіміки-теоретики Д.А. Бочвар і О.Г. Гальперн квантово-хімічними розрахунками підтвердили стабільність молекули С60, і лише у 1985 р. Р. Смоллі, Р. Керл та Г. Крото експериментально отримали кластери із 60 атомів вуглецю в стійкій формі, яку вони пояснили структурою молекули у вигляді футбольного м’яча. Натхненнику цього відкриття, видатному вченому, нобелівському лауреату, активному популяризатору нанотехнологій Річарду Смоллі присвячено цей матеріал.В сентябре этого года исполняется 27 лет с момента открытия фуллерена — новой сферообразной формы углерода. Это событие буквально потрясло ученых, которые в то время считали, что об элементарном углероде им известно практически все. История открытия этого вещества довольно необычна. Еще в 1971 г. возможность су ществования молекулы фуллерена была предсказана японским ученым Е. Осавой (E. Osawa), через два года советские химики-теоретики Д.А. Бочвар и Е.Г. Гальперн с помощью квантово-химических расчетов подтвердили стабильность молекулы С60, и только в 1985 г. Р. Смолли, Р. Керл и Г. Крото экспериментально получили кластеры из 60 атомов углерода в устойчивой форме, которую они объяснили структурой молекулы в виде футбольного мяча. Вдохновителю этого открытия, выдающемуся ученому, нобелевскому лауреату, активному популяризатору нанотехнологий Ричарду Смолли посвящен этот материал.27 years since the discovery of fullerene, the new form of carbon, is observed in September of this year. This event has literally shocked scientists, who believed at that time that they know almost everything about the elementary carbon. History of this discovery is rather unusual. Long ago, in 1971 the possibility of the existence of a fullerene molecule was predicted by an young Japanese scientist E. Osawa. Then two Soviet chemists and theorists D.A. Bochvar and E.G. Hal pern confirm the stability of the C60 molecule using quantum chemical calculations, and in 1985 at last R. Smalley, R. Curl and H. Kroto experimentally obtained clusters of 60 carbon atoms in a sustainable form. They explained the structure of this molecule as the structure of a soccer ball. This material is devoted to the inspirer of this discovery, an outstanding scientist, Nobel laureate, active popularizer of nanotechnology — Richard Smalley

Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease

The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn’s disease, ulcerative colitis (UC) and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL) for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner

Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago

Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world

IL-2 Regulates Expression of C-MAF in Human CD4 T Cells

Blockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2 responses in human T cells. Recent murine studies have shown that IL-2 also plays a significant role in regulating Th2 cell differentiation by activated STAT5. To explore the role of activated STAT5 in the Th2 differentiation of primary human T cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression. Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to specific sites in the C-MAF promoter. These sites corresponded to regions enriched for markers of chromatin architectural features in both resting CD4 and differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T cells with or without prior TCR stimulation. TCR-induced C-MAF expression was significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333. Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR-activated T cells, suggesting functional cooperation between these cytokines. Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus, our findings demonstrate the importance of IL-2 in Th2 differentiation in human T cells and support the notion that IL-2R–directed therapies may have utility in the treatment of allergic disorders

IUCF High Intensity Polarized Ion Source

This research was sponsored by the National Science Foundation Grant NSF PHY-931478