Past,present and future utilisation ofMyrica gale (Myricaceae)

The development ofM. gale oil as an insect repellent has created a requirement for cultivation of the plant. Botanical evidence indicates thatM. gale is likely to thrive on well—aerated acid peatland and could become a valuable crop on land of low agricultural value. Plant growth would be enhanced by the prevention of grazing and could be combined with softwood forestry since the trees would benefit from soil nitrogen enrichment thanks to the symbiotic association ofM. gale andFrankia. The economics of oil production would be improved if additional compounds of value such as pharmacologically active fiavonoids could be extracted from the by-products.     

Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

Nutritional Aspects of Dissimilatory Sulfate Reduction in the Human Large Intestine

In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group.  Experiments with two strains of Desulfovibrio desulfuricans isolated from human feces demonstrated that both were able to reduce sulfite, thiosulfate or nitrate in the absence of sulfate. In addition, one strain (DsvUC1) was able to grow by fermentative metabolism, although the second strain (DsvFD1) showed more restricted fermentative growth. The data indicate that desulfovibrios are ecologically the most significant group of SRB in the human colon, and that colonic isolates belonging to this genus are versatile, in terms of both the electron acceptors and donors that they are able to utilize. Received: 24 March 1997 / Accepted: 10 June 1997     

Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis

The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and bone pain. However, very little is known about the role of the skeletal CB2 receptor in the regulation of osteoblasts and osteoclasts changes associated with breast cancer. Here we found that the CB2-selective agonists HU308 and JWH133 reduced the viability of a variety of parental and bone-tropic human and mouse breast cancer cells at high micromolar concentrations. Under conditions in which these ligands are used at the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell-induced osteoclastogenesis and exacerbated osteolysis, and these effects were attenuated in cultures obtained from CB2-deficient mice or in the presence of a CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or differentiation in the presence of conditioned medium from breast cancer cells, but under these circumstances both agents enhanced parathyroid hormone-induced osteoblast differentiation and the ability to support osteoclast formation. Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133 and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects were enhanced in the presence of osteolytic and osteoblastic factors such as RANKL (receptor activator of NFκB ligand) and parathyroid hormone. When combined with published work, these findings suggest that breast cancer and bone cells exhibit differential responses to treatment with CB2 ligands depending upon cell type and concentration used. We, therefore, conclude that both CB2-selective activation and antagonism have potential efficacy in cancer-associated bone disease, but further studies are warranted and ongoing.     

Germination and Emergence of Primed Grass Seeds Under Field and Simulated-field Temperature Regimes

Seed priming may enhance establishment success of cool-seasonrange grasses which must compete with annual weeds for earlyspring moisture. Previous priming studies have confirmed germinationrate enhancement for these species but relative treatment effectsunder field-temperature conditions have not been assessed. Weprimed seeds of thickspike wheatgrass [Elymus lanceolatus(Scribn.and J. G. Smith) Gould], bluebunch wheatgrass [Pseudoroegneriaspicata(Pursh) Löve], Sandberg bluegrass (Poa sandbergiiVasey.) and bottlebrush squirreltail [Elymus elymoides(Raf.)Swezey] and evaluated their relative emergence rate in threesoil types as a function of spring-planting date. Germinationresponse was simultaneously evaluated in laboratory germinatorsthat were programmed to simulate the field-temperature regimeat planting depth. Seed priming enhanced both germination andemergence rate with the greatest effect occurring during theearlier, cooler planting dates. Total emergence and emergencerate in the field were lower than for the equivalent germinationresponse in the laboratory. Thermal-germination response wasmodelled and predictions developed for evaluating potentialgermination under late winter/early spring soil-temperatureregimes. Modelling results predicted that greater germinationenhancement would have been possible at earlier planting datesthan were measured in the field experiment.Copyright 2000 Annalsof Botany Company Bunchgrass, germination, emergence, priming, rate, temperature     

Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans

Coherence between the bioelectric activity of sensorimotor cortex and contralateral muscles can be observed around 20 Hz. By contrast, physiological tremor has a dominant frequency around 10 Hz. Although tremor has multiple sources, it is partly central in origin, reflecting a component of motoneuron discharge at this frequency. The motoneuron response to ∼20 Hz descending input could be altered by non-linear interactions with ∼10 Hz motoneuron firing. We investigated this further in eight healthy human subjects by testing the effects of the beta-adrenergic agents propranolol (non-selective β-antagonist) and salbutamol (β₂-agonist), which are known to alter the size of physiological tremor. Corticomuscular coherence was assessed during an auxotonic precision grip task; tremor was quantified using accelerometry during index finger extension. Experiments with propranolol used a double-blind, placebo-controlled crossover design. A single oral dose of propranolol (40 mg) significantly increased beta band (15.3–32.2 Hz) corticomuscular coherence compared with placebo, but reduced tremor in the 6.2–11.9 Hz range. Salbutamol (2.5 mg) was administered by inhalation. Whilst salbutamol significantly increased tremor amplitude as expected, it did not change corticomuscular coherence. The opposite direction of the effects of propranolol on corticomuscular coherence and tremor, and the fact that salbutamol enhances tremor but does not affect coherence, implies that the magnitude of corticomuscular coherence is little influenced by non-linear interactions with 10 Hz oscillations in motoneurons or the periphery. Instead, we suggest that propranolol and salbutamol may affect both tremor and corticomuscular coherence partly via a central site of action.     

Multipotent Cancer Stem Cells Derived from Human Malignant Peritoneal Mesothelioma Promote Tumorigenesis

During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression.