Inhibition kinetics of carba- and C-fucosyl analogues of GDP-fucose against fucosyltransferase V: implication for the reaction mechanism

Inhibition kinetics of two isosteric analogues of GDP-fucose (GDP-Fuc) were investigated against fucosyltransferase V using electrospray ionization mass spectrometry coupled to multiple reaction monitoring. The carba-Fuc analogue was found to be a competitive inhibitor with a K(i) value of 67.1+/-9.8 microM, similar to the K(m) value for GDP-Fuc (50.4+/-5.5 microM), while the C-Fuc analogue exhibited significantly weak competitive inhibition with a K(i) value of 889+/-93 microM.     

Tropical winter habitat limits reproductive success on the temperate breeding grounds in a migratory bird

Identifying the factors that control population dynamics in migratory animals has been constrained by our inability to track individuals throughout the annual cycle. Using stable carbon isotopes, we show that the reproductive success of a long-distance migratory bird is influenced by the quality of habitat located thousands of kilometres away on tropical wintering grounds. For male American redstarts (Setophaga ruticilla), winter habitat quality influenced arrival date on the breeding grounds, which in turn affected key variables associated with reproduction, including the number of young fledged. Based on a winter-habitat model, females occupying high-quality winter habitat were predicted to produce more than two additional young and to fledge offspring up to a month earlier compared with females wintering in poor-quality habitat. Differences of this magnitude are highly important considering redstarts are single brooded, lay clutches of only three to five eggs and spend only two-and-a-half months on the breeding grounds. Results from this study indicate the importance of understanding how periods of the annual cycle interact for migratory animals. Continued loss of tropical wintering habitat could have negative effects on migratory populations in the following breeding season, minimizing density-dependent effects on the breeding grounds and leading to further population declines. If conservation efforts are to be successful, strategies must incorporate measures to protect all the habitats used during the entire annual cycle of migratory animals.     

Dynamic patterns of growth hormone gene transcription in individual living pituitary cells

Real-time imaging of the GH gene promoter linked to luciferase in living pituitary cells has revealed surprising heterogeneity and variety of dynamic patterns of gene expression. Cells treated with either forskolin or thyroid hormone generated a consistent and characteristic temporal response from cell populations, but detailed analysis of individual cells revealed different patterns. Approximately 25-26% of cells displayed no response, 25-33% of cells exhibited a sustained progressive rise in luciferase activity, and 41-50% showed a transient phasic, or oscillatory response, after given stimuli. In cells treated consecutively with the two stimuli, the population response to the second stimulus was augmented. Single-cell analysis revealed that this was partly due to an increased number of cells responding, but also that the prevalence of response patterns changed: cells that responded to an initial stimulus were more likely to respond subsequently in a progressive sustained manner. In conclusion, these studies have indicated that GH promoter activity in individual living pituitary cells is unstable and possibly stochastic, with dynamic variations from hour to hour. The prevalence of different temporal patterns of response to hormonal stimulation among a population of cells is altered by the endocrine history of those cells.     

Vibration training: an overview of the area, training consequences, and future considerations

The effects of vibration on the human body have been documented for many years. Recently, the use of vibration for improving the training regimes of athletes has been investigated. Vibration has been used during strength-training movements such as elbow flexion, and vibration has also been applied to the entire body by having subjects stand on vibration platforms. Exposure to whole-body vibration has also resulted in a significant improvement in power output in the postvibratory period and has been demonstrated to induce significant changes in the resting hormonal profiles of men. In addition to the potential training effects of vibration, the improvement in power output that is observed in the postvibratory period may also lead to better warm-up protocols for athletes competing in sporting events that require high amounts of power output. These observations provide the possibility of new and improved methods of augmenting the training and performance of athletes through the use vibration training. Despite the potential benefits of vibration training, there is substantial evidence regarding the negative effects of vibration on the human body. In conclusion, the potential of vibration treatment to enhance the training regimes of athletes appears quite promising. It is essential though that a thorough understanding of the implications of this type of treatment be acquired prior to its use in athletic situations. Future research should be done with the aim of understanding the biological effects of vibration on muscle performance and also the effects of different vibration protocols on muscle performance.     

Crystal structure of methyl 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranuronate

The identity of the crystalline product formed by the acetylation of a mixture of methyl alpha- and beta-D-glucopyranuronates has been confirmed as being methyl 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranuronate (3), which agrees with the assignment from 1H NMR. The absolute configuration of compound 3 was assigned to agree with the known chirality of the precursor sugar, D-glucono-6,3-lactone.     

Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family kinase p56(Lck)

We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group.     

Chemical variation in the tropical seaweed Stypopodium zonale (dictyotaceae)

Five separate collections of the tropical seaweed Stypopodium zonale were analysed for ten secondary metabolites using a combination of high performance liquid chromatography and proton nuclear magnetic resonance spectrometry. Shallow water populations from the Caribbean were found to possess similar metabolite profiles from year to year and from widely diverse locations. Stypopodium zonale from the South Pacific (Palau) contained similar structure types; however, the profile was qualitatively and quantitatively dissimilar to the Caribbean algae. A deep water Caribbean form of S. zonale was found to contain two metabolites, epitaondiol and 6a-desmethyl-6-acetylatomaric acid, not observed in the other extracts. This latter population is morphologically and anatomically distinct from the other S. zonale Caribbean populations.     

Decision Analysis Frameworks for Life-Cycle Impact Assessment

Life‐cycle impact assessments (LCIAs) are complex because they almost always involve uncertain consequences relative to multiple criteria. Several authors have noticed that this is precisely the sort of problem addressed by methods of decision analysis. Despite several experiences of using multipleattribute decision analysis (MADA) methods in LCIA, the possibilities of MADA methods in LCIA are rather poorly elaborated in the field of life‐cycle assessment. In this article we provide an overview of the commonly used MADA methods and discuss LCIA in relation to them. The article also presents how different frames and tools developed by the MADA community can be applied in conducting LCIAs. Although the exact framing of LCIA using decision analysis still merits debate, we show that the similarities between generic decision analysis steps and their LCIA counterparts are clear. Structuring of an assessment problem according to a value tree offers a basis for the definition of impact categories and classification. Value trees can thus be used to ensure that all relevant impact categories and interventions are taken into account in the appropriate manner. The similarities between multiattribute value theory (MAVT) and the current calculation rule applied in LCIA mean that techniques, knowledge, and experiences derived from MAVT can be applied to LCIA. For example, MAVT offers a general solution for the calculation of overall impact values and it can be applied to help discern sound from unsound approaches to value measurement, normalization, weighting, and aggregation in the LCIA model. In addition, the MAVT framework can assist in the methodological development of LCIA because of its well‐established theoretical foundation. The relationship between MAVT and the current LCIA methodology does not preclude application of other MADA methods in the context of LCIA. A need exists to analyze the weaknesses and the strengths of different multiple‐criteria decision analysis methods in order to identify those methods most appropriate for different LCIA applications.