Fluoxetine-resistance genes in Caenorhabditis elegans function in the intestine and may act in drug transport

Fluoxetine (Prozac) is one of the most widely prescribed pharmaceuticals, yet important aspects of its mechanism of action remain unknown. We previously reported that fluoxetine and related antidepressants induce nose muscle contraction of C. elegans. We also reported the identification and initial characterization of mutations in seven C. elegans genes that cause defects in this response (Nrf, nose resistant to fluoxetine). Here we present genetic evidence that the known nrf genes can be divided into two subgroups that confer sensitivity to fluoxetine-induced nose contraction by distinct pathways. Using both tissue-specific promoters and genetic mosaic analysis, we show that a gene from one of these classes, nrf-6, functions in the intestine to confer fluoxetine sensitivity. Finally, we molecularly identify nrf-5, another gene in the same class. The NRF-5 protein is homologous to a family of secreted lipid-binding proteins with broad ligand specificity. NRF-5 is expressed in the intestine and is likely secreted into the pseudocoelomic fluid, where it could function to transport fluoxetine. One model that explains these findings is that NRF-5 binds fluoxetine and influences its presentation or availability to in vivo targets.     

Avian predation on a parasitic fly of cervids during winter: can host‐related cues increase the predation risk?

The deer ked (Lipoptena cervi) is an ectoparasitic fly on cervids that has expanded its distribution rapidly in Northern Europe. However, the regulating biotic factors such as predation remain unknown. The host‐independent pupal stage of the fly lasts for several months. Blackish pupae are visible against snow, especially on the bedding sites of hosts, and are thus exposed to predators. To evaluate the role of predation on the invasion dynamics and evolution of L. cervi, we monitored pupal predation on artificial bedding sites in three geographical areas in Finland during winter. We explored: (1) possible predators; (2) magnitude of predation; and (3) whether predation risk is affected by host‐derived cues. We demonstrate that pupae are predated by a number of tit species. Any reddish brown snow discoloration on bedding sites, indicating heavy infestation of the host, serves as an exploitable cue for avian predators, thereby increasing the risk of pupal predation. The ability of tits to use this host‐derived cue seems to be dependent on the prevalence of L. cervi and the period of invasion history, which suggests that it may be a learned behavioural response. Predation by tits may potentially affect the L. cervi population dynamics locally. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 106 , 275–286.     

Short‐term soil carbon sink potential of oil palm plantations

Oil palm plantations cover ≈14.6 million ha worldwide and the total area under cultivation is expected to increase during the 21st century . Indonesia and Malaysia together account for 87% of global palm oil production and the combined harvested area in these countries has expanded by 6.5 million ha since 1990. Despite this, soil C cycling in oil palm systems is not well quantified but such information is needed for C budget inventories. We quantified soil C storage (root biomass, soil organic matter (SOM) and microbial biomass) and losses [potential soil respiration (R_s) and soil surface CO₂ flux (F_s)] in mineral soils from an oil palm plantation chronosequence (11–34 years since planting) in Selangor, Malaysia. There were no significant effects of plantation age on SOM, microbial biomass, R_s or F_s, implying soil C was in dynamic equilibrium over the chronosequence. However, there was a significant increase in root biomass with plantation age, indicating a short‐term C sink. Across the chronosequence, R_s was driven by soil moisture, soil particle size, root biomass and soil microbial biomass N but not microbial biomass C. This suggests that the nutrient status of the microbial community may be of equal or greater importance for soil CO₂ losses than substrate availability and also raises particular concerns regarding the addition of nitrogenous fertilizer, i.e. increased yields will be associated with increased soil CO₂ emissions. To fully assess the impact of oil palm plantations on soil C storage, initial soil C losses following land conversion (e.g. from native forest or other previous plantations) must be accounted for. If initial soil C losses are large, our data show that there is no accumulation of stable C in the soil as the plantation matures and hence the conversion to oil palm would probably represent a net loss of soil C.     

Interleukin-8 is the single most up-regulated gene in whole genome profiling of <Emphasis Type="Italic">H. pylori</Emphasis> exposed gastric epithelial cells

Background  

The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA^- H. pylori variants.     

In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis

Among sensory systems, the somatic sense is exceptional in its ability to detect a wide range of chemical, mechanical and thermal stimuli. How this sensory diversity is established during development remains largely elusive. We devised a method (BAPTISM) that uses the photoconvertible fluorescent protein Kaede to simultaneously analyze birthdate and cell fate in live zebrafish embryos. We found that trigeminal sensory ganglia are formed from early-born and late-born neurons. Early-born neurons give rise to multiple classes of sensory neurons that express different ion channels. By contrast, late-born neurons are restricted in their fate and do not form chemosensory neurons expressing the ion channel TrpA1b. Accordingly, larvae lacking early-born neurons do not respond to the TrpA1b agonist allyl isothiocyanate. These results indicate that the multimodal specification and function of trigeminal sensory ganglia depends on the timing of neurogenesis.     

Biosynthetic regulation of monobutyrin, an adipocyte-secreted lipid with angiogenic activity

1-Butyrylglycerol (monobutyrin) is a novel angiogenic compound that is synthesized and secreted during the differentiation of 3T3-F442A preadipocytes into adipocytes. To study the regulation of monobutyrin biosynthesis we have developed an assay utilizing the lgycerol kinase enzyme from Cellulomonas to quantitate the levels of this compound in cell-conditioned medium. Analysis of several cultured cell types, including tumor cell lines, indicated that monobutyrin production is detectable only from adipocytes, reaching a steady-state concentration of approximately 1.0 microM in conditioned medium. Monobutyrin synthesis was demonstrated in vitro using [14C]butyryl-CoA with total homogenate or particulate fractions from adipocytes. Similar fractions from non-adipocyte cell lines failed to synthesize monobutyrin. This biosynthetic activity was shown to be distinct by substrate competition studies from the microsomal sn-glycerol-3-phosphate acyltransferase, whose activity is known to increase during adipocyte differentiation. The production of monobutyrin was hormonally regulated, as the addition of epinephrine to adipocytes caused a 10-fold increase in the amount of monobutyrin secreted. These results indicate that monobutyrin synthesis is adipocyte specific, occurs through an apparently novel particulate enzyme system, and is regulated in a hormone-dependent manner. The implications of these results for adipose physiology and angiogenesis are discussed.