Inorganic N addition replaces N supplied to switchgrass (Panicum virgatum) by arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal fungi (AMF) provide many benefits in agroecosystems including improved soil tilth, carbon sequestration, and water and nutrient transfer to plants. AMF are known to affect plant nitrogen (N) dynamics and transfer N to plants, but there have been few studies addressing whether the amount of N transferred to plants by AMF is agronomically relevant. We used δ15 N natural abundance methods and δ15 N mass balance equations to estimate the amount of plant N derived from AMF transfer in perennial grasses managed for bioenergy production under different N addition treatments (0, 56, and 196 kg N/ha). Differentiation of δ15 N among plant, soil N, and AMF pools was higher than anticipated leading to calculations of 34-55% of plant N transferred by AMF in the treatments receiving no N addition to 6-22% of plant N transferred to plants in high-N addition treatments. AMF extra-radical hyphae biomass was significantly reduced in the high-N (196 kg N/ha) addition treatments, which was negatively correlated to enriched plant δ15 N. Our results suggest that N addition decreases AMF N transfer to plants. When N was limiting to plant growth, AMF supplied agronomically significant amounts of plant N, and a higher proportion of overall plant N. Because differentiation between N pools was greater than expected, stable isotope measurements can be used to estimate N transfer to AMF plant hosts.

Targeting of the circadian clock via CK1δ/ε to improve glucose homeostasis in obesity.

Growing evidence indicates that disruption of our internal timing system contributes to the incidence and severity of metabolic diseases, including obesity and type 2 diabetes. This is perhaps not surprising since components of the circadian clockwork are tightly coupled to metabolic processes across the body. In the current study, we assessed the impact of obesity on the circadian system in mice at a behavioural and molecular level, and determined whether pharmacological targeting of casein kinase 1δ and ε (CK1δ/ε), key regulators of the circadian clock, can confer metabolic benefit. We demonstrate that although behavioural rhythmicity was maintained in diet-induced obesity (DIO), gene expression profiling revealed tissue-specific alteration to the phase and amplitude of the molecular clockwork. Clock function was most significantly attenuated in visceral white adipose tissue (WAT) of DIO mice, and was coincident with elevated tissue inflammation, and dysregulation of clock-coupled metabolic regulators PPARα/γ. Further, we show that daily administration of a CK1δ/ε inhibitor (PF-5006739) improved glucose tolerance in both DIO and genetic (ob/ob) models of obesity. These data further implicate circadian clock disruption in obesity and associated metabolic disturbance, and suggest that targeting of the clock represents a therapeutic avenue for the treatment of metabolic disorders.

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial.

BACKGROUND: Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction ('optical treatment') followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching ('dose'), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. METHODS/DESIGN: A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. DISCUSSION: This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome. TRIAL REGISTRATION: ISRCTN ISRCTN12292232.

Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing.

Eri1 is a 3'-to-5' exoribonuclease conserved from fission yeast to humans. Here we show that Eri1 associates with ribosomes and ribosomal RNA (rRNA). Ribosomes from Eri1-deficient mice contain 5.8S rRNA that is aberrantly extended at its 3' end, and Eri1, but not a catalytically inactive mutant, converts this abnormal 5.8S rRNA to the wild-type form in vitro and in cells. In human and murine cells, Eri1 localizes to the cytoplasm and nucleus, with enrichment in the nucleolus, the site of preribosome biogenesis. RNA binding residues in the Eri1 SAP and linker domains promote stable association with rRNA and thereby facilitate 5.8S rRNA 3' end processing. Taken together, our findings indicate that Eri1 catalyzes the final trimming step in 5.8S rRNA processing, functionally and spatially connecting this regulator of RNAi with the basal translation machinery.

Dietary fish oil deactivates a growth-promoting signaling pathway in hepatoma 7288CTC in Buffalo rats.

Dietary fish oil decreases growth of solid tumors in rodents. Mechanisms for this effect are not well defined. In rat hepatoma 7288CTC, short-term (1-2 h) treatment with eicosapentaenoic acid during perfusion in situ reduced fatty acid uptake and [(3)H]thymidine incorporation. To determine if dietary fish oil had this effect in vivo, 48 male Buffalo rats were implanted with tissue-isolated hepatoma 7288CTC and were divided into three groups: Diet I (8% olive oil/2% corn oil), Diet II (6% olive oil/2% corn oil/2% fish oil), or Diet III (3% olive oil/3% corn oil/4% fish oil). When tumors weighed 4 to 6 g rats were anesthetized and tumor fatty acid uptake and 13-hydroxyoctadecadienoic acid release were measured in vivo by arterial minus venous differences. Tumors were analyzed for cyclic adenosine monophosphate (cAMP), DNA content, and [(3)H]thymidine incorporation. Fish oil feeding significantly (P < 0.05) reduced tumor growth, cAMP content, fatty acid uptake, 13-hydroxyoctadecadienoic acid formation, DNA content, and [(3)H]thymidine incorporation. Addition of either pertussis toxin or 8-bromoadenosine-cAMP to the arterial blood reversed the inhibitions in tumors in rats fed diet II. These results provide in vivo evidence that dietary fish oil suppressed a specific linoleic acid-dependent, inhibitory G protein-coupled, growth-promoting signaling pathway in rat hepatoma 7288CTC.

Perceived quality of life: a neglected component of adolescent health assessment and intervention.

The contribution of the construct of perceived quality of life (PQOL) to adolescent health assessment and promotion is discussed. Theory, measurement, and correlates of PQOL in adolescence are reviewed, with a focus on the incremental validity of PQOL data in relationship to more traditional pathology-based health indices. Similar to Diener's proposal, which pertained exclusively to adults, we call for the inclusion of PQOL data in national databases that monitor adolescent health outcomes.

Physiologic melatonin concentration, omega-3 fatty acids, and conjugated linoleic acid inhibit fatty acid transport in rodent hind limb skeletal muscle in vivo.

Melatonin (MLT), the circadian neurohormone secreted by the pineal gland in mammals during darkness, eicosapentanoic acid (EPA), and conjugated linoleic acid (CLA) have established regulatory roles in cancer growth. Investigations in our laboratory have indicated that these agents inhibit fatty acid (FA) transport by tumors and several sub-types of white adipose tissue via inhibitory G protein-coupled receptor mechanisms. Skeletal muscle constitutes over 45% of human body mass and plays an important role in cancer cachexia and obesity-related diseases. Since fatty acid oxidation is a major source of energy for this tissue, we tested the hypothesis that physiologic MLT levels, EPA, or CLA injected intravenously, inhibit FA uptake in rat skeletal muscle in vivo. We used a surgical technique for catheterizing the femoral vein in rats that allows rapid blood collection from the entire hind limb, while ensuring continuous blood flow to the tissue. Blood acid/gas tensions and hematocrit were monitored and remained constant during the course of each experiment. The MLT, EPA, and CLA inhibited FA uptake by the tissue and lowered cAMP values. Glucose uptake and glycerol production in the hind limb were not affected. These investigations suggest a novel role for MLT, omega-3 FAs, and CLA in the regulation of FA transport and fat metabolism in skeletal muscle.

Sensitivity of cyanobacterial antenna, reaction center and CO2 assimilation transcripts and proteins to moderate UVB: light acclimation potentiates resistance to UVB.

We tested the hypothesis that cyanobacterial cells have sufficient acclimation potential to tolerate UVB when it is applied in a natural quantum ratio to growth photosynthetically active radiation (PAR). We grew Synechococcus under 50 (Low) or 300 (High) micromol PAR m(-2) x s(-1) and then exposed the cells to 0.125 (Low) or 0.75 (High) micromol UVB m(-2) x s(-1). The PAR:UVB quantum ratios were near natural for both the Low-PAR:Low-UVB and the High-PAR:High-UVB treatments, but UVB was in excess of typical aquatic PAR:UVB for Low-PAR:High-UVB treatments. The cellular light history determined the UVB responses of Synechococcus. High-PAR cells initially had fewer cpc transcripts encoding phycocyanin, lower phycocyanin content, and more psbAII/AIII transcripts encoding the D1:2 photosystem II (PSII) protein isoform. Higher PAR potentiated them to tolerate an appropriate UVB level without short-term inhibition of PSII or growth. Low-PAR cells rapidly altered psbAII/AIII and cpc gene expression and tolerated appropriate Low UVB. Low-PAR:High-UVB cells, in contrast, suffered short-term inhibition of PSII and growth. In all treatments UVB induced transient loss of cpc transcripts, possibly to free resources for psbAII/AIII expression, which is important for UVB resistance. The drop in cpc transcripts was not part of a general shock response because rbcL transcript pools were stable upon UVB exposure.