Genetic Structure of Modern Durum Wheat Cultivars and Mediterranean Landraces Matches with Their Agronomic Performance

A collection of 172 durum wheat landraces from 21 Mediterranean countries and 20 modern cultivars were phenotyped in 6 environments for 14 traits including phenology, biomass, yield and yield components. The genetic structure of the collection was ascertained with 44 simple sequence repeat markers that identified 448 alleles, 226 of them with a frequency lower than 5%, and 10 alleles per locus on average. In the modern cultivars all the alleles were fixed in 59% of the markers. Total genetic diversity was HT = 0.7080 and the genetic differentiation value was GST = 0.1730. STRUCTURE software allocated 90.1% of the accessions in five subpopulations, one including all modern cultivars, and the four containing landrace related to their geographic origin: eastern Mediterranean, eastern Balkans and Turkey, western Balkans and Egypt, and western Mediterranean. Mean yield of subpopulations ranged from 2.6 t ha-1 for the western Balkan and Egyptian landraces to 4.0 t ha-1 for modern cultivars, with the remaining three subpopulations showing similar values of 3.1 t ha-1. Modern cultivars had the highest number of grains m-2 and harvest index, and the shortest cycle length. The diversity was lowest in modern cultivars (HT = 0.4835) and highest in landraces from the western Balkans and Egypt (HT = 0.6979). Genetic diversity and AMOVA indicated that variability between subpopulations was much lower (17%) than variability within them (83%), though all subpopulations had similar biomass values in all growth stages. A dendrogram based on simple sequence repeat data matched with the clusters obtained by STRUCTURE, improving this classification for some accessions that have a large admixture. landraces included in the subpopulation from the eastern Balkans and Turkey were separated into two branches in the dendrogram drawn with phenotypic data, suggesting a different origin for the landraces collected in Serbia and Macedonia. The current study shows a reliable relationship between genetic and phenotypic population structures, and the connection of both with the geographic origin of the landraces.The research was funded by the Ministerio de Economía y competitividad project AGL-2006-09226-C02-01, and Dr. Jose Miguel Soriano is funded by Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (http://www.mineco.gob.es/)

The Human Sweet Tooth

Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries

Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial

Frank L Lanza,1 Agron Collaku,2 Dongzhou J Liu3 1Department of Gastroenterology, Houston Institute for Clinical Research, Houston, TX, USA; 2Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA; 3Global Clinical Development, GlaxoSmithKline, Collegeville, PA, USA Background: While gastrointestinal (GI) effects of standard ibuprofen and N-acetyl-p-­aminophenol (APAP) have been reported, upper GI injury following treatment with fast-dissolving (FD) formulations of these analgesics has not been investigated. We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product. Methods: In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID), ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID), and placebo 2×500 mg tablets QID for 7 days. The primary end point was gastric mucosal damage assessed by endoscopy using the Lanza scale: 0=normal stomach or proximal duodenum, 1=mucosal hemorrhages only, 2=1 or 2 erosions, 3=numerous (3–10) erosions, and 4=large number of erosions (>10) or ulcer. Secondary end points included duodenal mucosal damage (Lanza scale); gastroduodenal mucosal injury, classified as present (gastric and/or duodenal endoscopy score ≥2) or absent (gastric and/or duodenal endoscopy score <2); and number of hemorrhages, erosions, and ulcers counted separately in the stomach and duodenum. Results: Significantly greater gastric mucosal injury was observed after treatment with both ibuprofen products vs FD-APAP (p<0.0001 and p=0.0095, respectively). FD-APAP showed no difference from placebo (p=0.4794). The odds of having an incidence of gastroduodenal mucosal injury were over 6 times greater from FD ibuprofen liquid capsule treatment (odds ratio [OR]=6.19, 95% confidence interval [CI]: 1.60, 23.97) and over 3 times greater from ibuprofen tablet treatment (OR=3.19, 95% CI: 0.8, 12.74) vs FD-APAP. Conclusion: Treatment with 2 ibuprofen products was associated with significant gastric mucosal injury. Of the 4 treatments studied, FD ibuprofen liquid capsules had the highest risk of incidence of gastroduodenal mucosal injury. Treatment with FD-APAP did not induce any clinically or statistically significant gastroduodenal mucosal injury. Keywords: gastric mucosal damage, APAP, NSAIDs, erosions, hemorrhages, ulce

Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

Agron Collaku, Yong Yue, Kenneth Reed GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA Background/objective: Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods: This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0= not present to 10= unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. Results: A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Conclusion: Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed. Keywords: guaifenesin, upper back pain, muscle spasm, muscle relaxation, Vernon–Mior disability assessmen

Design and Integration of the EU-DEMO Water-Cooled Lead Lithium Breeding Blanket

The water-cooled lead lithium breeding blanket (WCLL BB) is one of two BB candidate concepts to be chosen as the driver blanket of the EU-DEMO fusion reactor. Research activities carried out in the past decade, under the umbrella of the EUROfusion consortium, have allowed a quite advanced reactor architecture to be achieved. Moreover, significant efforts have been made in order to develop the WCLL BB pre-conceptual design following a holistic approach, identifying interfaces between components and systems while respecting a system engineering approach. This paper reports a description of the current WCLL BB architecture, focusing on the latest modifications in the BB reference layout aimed at evolving the design from its pre-conceptual version into a robust conceptual layout. In particular, the main rationale behind design choices and the BB’s overall performances are highlighted. The present paper also gives an overview of the integration between the BB and the different in-vessel systems interacting with it. In particular, interfaces with the tritium extraction and removal (TER) system and the primary heat transfer system (PHTS) are described. Attention is also paid to auxiliary systems devoted to heat the plasma, such as electron cyclotron heating (ECH). Indeed, the integration of this system in the BB will strongly impact the segment design since it envisages the introduction of significant cut-outs in the BB layout. A preliminary CAD model of the central outboard blanket (COB) segment housing the ECH cut-out has been set up and is reported in this paper. The chosen modeling strategy, adopted loads and boundary conditions, as well as obtained results, are reported in the paper and critically discussed