The identification of a selective dopamine D2 partial agonist,D3 antagonist displaying high levels of brain exposure

The identification of a highly selective D₂ partial agonist, D₃ antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.     

The macronutrient composition of wild and cultivated plant foods of West African chimpanzees (Pan troglodytes verus) inhabiting an anthropogenic landscape

Agricultural expansion encroaches on tropical forests and primates in such landscapes frequently incorporate crops into their diet. Understanding the nutritional drivers behind crop-foraging can help inform conservation efforts to improve human-primate coexistence. This study builds on existing knowledge of primate diets in anthropogenic landscapes by estimating the macronutrient content of 24 wild and 11 cultivated foods (90.5% of food intake) consumed by chimpanzees (Pan troglodytes verus) at Bossou, Guinea, West Africa. We also compared the macronutrient composition of Bossou crops to published macronutrient measures of crops from Bulindi, Uganda, East Africa. The composition of wild fruits, leaves, and pith were consistent with previous reports for primate diets. Cultivated fruits were higher in carbohydrates and lower in insoluble fiber than wild fruits, while wild fruits were higher in protein. Macronutrient content of cultivated pith fell within the ranges of consumed wild pith. Oil palm food parts were relatively rich in carbohydrates, protein, lipids, and/or fermentable fiber, adding support for the nutritional importance of the oil palm for West African chimpanzees. We found no differences in the composition of cultivated fruits between Bossou and Bulindi, suggesting that macronutrient content alone does not explain differences in crop selection. Our results build on the current understanding of chimpanzee feeding ecology within forest-agricultural mosaics and provide additional support for the assumption that crops offer primates energetic benefits over wild foods.     

Fiber type composition of four hindlimb muscles of adult Fisher 344 rats

 The limb and trunk muscles of adult rats express four myosin heavy chain (MHC) isoforms, one slow (MHCI) and three fast (MHCIIa, MHCIId, and MHCIIb). The distribution of these isoforms correlates with fiber types delineated using myofibrillar actomyosin adenosine triphosphatase (mATPase) histochemistry. For example, type I fibers express MHCI and fiber types IIA, IID, and IIB express MHCIIa, MHCIId, and MHCIIb, respectively. Fibers containing only one MHC isoform have been termed ”pure” fibers. Recent evidence suggests that a population of ”hybrid” fibers exist in rat skeletal muscle which contain two MHC isoforms. The purpose of the present investigation was to document the entire range of histochemically defined ”pure” and ”hybrid” fiber types in untreated muscles of the young adult Fisher 344 rat hindlimb. The selected hindlimb muscles (soleus, tibialis anterior, extensor digitorum longus, and gastrocnemius muscles) were removed from 12 male rats and analyzed for muscle fiber type distribution, cross-sectional area, and MHC content. Care was taken to delineate eight fiber types (I, IC, IIC, IIA, IIAD, IID, IIDB, and IIB) using refined histochemical techniques. Hybrid fibers were found to make up a considerable portion of the muscles examined (a range of 8.8–17.8% of the total). The deep red portion of the gastrocnemius muscle contained the largest number of hybrid fibers, most of which were the fast types IIAD (8.5±2.8%) and IIDB (5.2±2.3%). In conclusion, hybrid fibers make up a considerable portion of normal rat limb musculature and are an important population that should not be ignored. Accepted: 15 October 1998     

Identification of a specific isoform of tomato lipoxygenase (TomloxC) involved in the generation of fatty acid-derived flavor compounds

There are at least five lipoxygenases (TomloxA, TomloxB, TomloxC, TomloxD, and TomloxE) present in tomato (Lycopersicon esculentum Mill.) fruit, but their role in generation of fruit flavor volatiles has been unclear. To assess the physiological role of TomloxC in the generation of volatile C6 aldehyde and alcohol flavor compounds, we produced transgenic tomato plants with greatly reduced TomloxC using sense and antisense constructs under control of the cauliflower mosaic virus 35S promoter. The expression level of the TomloxC mRNA in some transgenic plants was selectively reduced by gene silencing or antisense inhibition to between 1% and 5% of the wild-type controls, but the expression levels of mRNAs for the four other isoforms were unaffected. The specific depletion of TomloxC in transgenic tomatoes led to a marked reduction in the levels of known flavor volatiles, including hexanal, hexenal, and hexenol, to as little as 1.5% of those of wild-type controls following maceration of ripening fruit. Addition of linoleic or linolenic acid to fruit homogenates significantly increased the levels of flavor volatiles, but the increase with the TomloxC-depleted transgenic fruit extracts was much lower than with the wild-type control. Confocal imaging of tobacco (Nicotiana tabacum) leaf cells expressing a TomloxC-GFP fusion confirmed a chloroplast localization of the protein. Together, these results suggest that TomloxC is a chloroplast-targeted lipoxygenase isoform that can use both linoleic and linolenic acids as substrates to generate volatile C6 flavor compounds. The roles of the other lipoxygenase isoforms are discussed.     

The impact of species concept on biodiversity studies

Species are defined using a variety of different operational techniques. While discussion of the various methodologies has previously been restricted mostly to taxonomists, the demarcation of species is also crucial for conservation biology. Unfortunately, different methods of diagnosing species can arrive at different entities. Most prominently, it is widely thought that use of a phylogenetic species concept may lead to recognition of a far greater number of much less inclusive units. As a result, studies of the same group of organisms can produce not only different species identities but also different species range and number of individuals. To assess the impact of different definitions on conservation issues, we collected instances from the literature where a group of organisms was categorized both under phylogenetic and nonphylogenetic concepts. Our results show a marked difference, with surveys based on a phylogenetic species concept showing more species (48%) and an associated decrease in population size and range. We discuss the serious consequences of this trend for conservation, including an apparent change in the number of endangered species, potential political fallout, and the difficulty of deciding what should be conserved.     

Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase

A set of trimeric and tetrameric derivatives 6-11 of the influenza virus neuraminidase inhibitor zanamivir 1 have been synthesized by coupling a common monomeric zanamivir derivative 3 onto various multimeric carboxylic acid core groups. These discrete multimeric compounds are all significantly more antiviral than zanamivir and also show outstanding long-lasting protective activity when tested in mouse influenza infectivity experiments.     

The gene ontology categorizer

The Gene Ontology Categorizer, developed jointly by the Los Alamos National Laboratory and Procter & Gamble Corp., provides a capability for the categorization task in the Gene Ontology (GO): given a list of genes of interest, what are the best nodes of the GO to summarize or categorize that list? The motivating question is from a drug discovery process, where after some gene expression analysis experiment, we wish to understand the overall effect of some cell treatment or condition by identifying 'where' in the GO the differentially expressed genes fall: 'clustered' together in one place? in two places? uniformly spread throughout the GO? 'high', or 'low'? In order to address this need, we view bio-ontologies more as combinatorially structured databases than facilities for logical inference, and draw on the discrete mathematics of finite partially ordered sets (posets) to develop data representation and algorithms appropriate for the GO. In doing so, we have laid the foundations for a general set of methods to address not just the categorization task, but also other tasks (e.g. distances in ontologies and ontology merger and exchange) in both the GO and other bio-ontologies (such as the Enzyme Commission database or the MEdical Subject Headings) cast as hierarchically structured taxonomic knowledge systems.     

The value of biodiversity experiments

Recent biodiversity experiments have investigated the relationship between diversity and ecosystem functioning by synthesizing plant communities from pools of species that have been experimentally manipulated to vary numbers and types of species present while holding abiotic factors constant. Biodiversity experiments therefore focus on a previously under-explored aspect of global change: the feedback from diversity to environment. Consequences of random manipulation of species communities may not correspond well to those of specific extinction sequences observed in the past in response to extinction drivers that cause highly non-random loss. However, random manipulation provides a good starting point given that existing communities could undergo many alternative orders of species loss in the future in response to a variety of different potential extinction drivers. Further, the effects of some extinction drivers are currently poorly understood and therefore difficult to predict (e.g. climate change) and it may be premature to dismiss the predictions of random scenarios as irrelevant to all real examples of species loss. The first generations of biodiversity experiments have provided valuable, and sometimes unexpected, discoveries about the general nature of the relationship between diversity and ecosystem functioning. These discoveries could not have been made using observational studies. We propose that different examples of extinction loss in the real or a potential future world form a continuum from situations where the results of the first-generation biodiversity experiments will be highly relevant to less relevant. At the one extreme are examples where the effects of biodiversity on ecosystem functioning will be overwhelmed by direct effects of the extinction driver on processes (e.g. chronic eutrophication). At the other extreme are situations where ecosystem processes are not strongly affected by direct effects of the extinction driver and where the effects of species loss on functioning may be more important (e.g. habitat fragmentation). Given the unprecedented uncertainty about the future of biodiversity and the functioning of ecosystems, a general approach with randomly varying species pools was the right place to start in order to provide a general foundation. The new challenge is to test for effects of biodiversity on functioning in real-world examples of species loss.

Zusammenfassung

Biodiversitätsversuche zeichnen sich dadurch aus, dass natürliche Artenpools experimentell reduziert werden und anschließend der Zusammenhang zwischen der Artenzahl und Ökosystemfunktionen unter konstanten abiotischen Umweltbedingungen untersucht wird. Dadurch unterscheiden sich Biodiversitätsexperimente grundsätzlich von anderen Versuchen, die die Biodiversität als Zielvariable behandeln und stattdessen die abiotische Umwelt manipulieren. Die Auswahl der Arten für die reduzierten Artenpools in Biodiversitätsexperimenten erfolgte bisher meist zufällig, während natürliche Aussterbefaktoren wie Eutrophierung nicht alle Arten gleichermassen gefährden. Für verschiedene Aussterbefaktoren ist aber so wenig bekannt, dass ein zufälliges Aussterbeszenario die beste gegenwärtig verfügbare Option ist. Dies trifft insbesondere für mögliche zukünftige Aussterbeprozesse zu, die durch globale Umweltveränderungen (Klima, biologische Invasionen) oder Habitatsfragmentierung ausgelöst werden könnten. Die erste Generation von Biodiversitätsexperimenten mit zufälligen Aussterbeszenarien hat wertvolle, teilweise unerwartete, generelle Zusammenhänge zwischen Artenzahl und Ökosystemfunktionen aufgedeckt. Diese Zusammenhänge ließen sich durch vergleichende Studien nicht erkennen. In Zukunft sollten Biodiversitätsexperimente dennoch vermehrt Aussterbeszenarien simulieren, die in der realen Umwelt mit größter Wahrscheinlichkeit auftreten.     

Fitness reduction and potential extinction of wild populations of Atlantic salmon, Salmo salar, as a result of interactions with escaped farm salmon

The high level of escapes from Atlantic salmon farms, up to two million fishes per year in the North Atlantic, has raised concern about the potential impact on wild populations. We report on a two-generation experiment examining the estimated lifetime successes, relative to wild natives, of farm, F(1) and F(2) hybrids and BC(1) backcrosses to wild and farm salmon. Offspring of farm and "hybrids" (i.e. all F(1), F(2) and BC(1) groups) showed reduced survival compared with wild salmon but grew faster as juveniles and displaced wild parr, which as a group were significantly smaller. Where suitable habitat for these emigrant parr is absent, this competition would result in reduced wild smolt production. In the experimental conditions, where emigrants survived downstream, the relative estimated lifetime success ranged from 2% (farm) to 89% (BC(1) wild) of that of wild salmon, indicating additive genetic variation for survival. Wild salmon primarily returned to fresh water after one sea winter (1SW) but farm and 'hybrids' produced proportionately more 2SW salmon. However, lower overall survival means that this would result in reduced recruitment despite increased 2SW fecundity. We thus demonstrate that interaction of farm with wild salmon results in lowered fitness, with repeated escapes causing cumulative fitness depression and potentially an extinction vortex in vulnerable populations.