Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 +/- 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses (P < 0.05), and renal angiotensinogen mRNA levels were approximately 2.6-fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were approximately two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 +/- 6.5 to 53.7 +/- 10.2%), did not return to control levels (36.1 +/- 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 +/- 25 to 261 +/- 75 mumol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.     

Metal biosorption in lignocellulosic biofuel biorefinery effluent: an initial step towards sustainability of water resources

Biosorption of metals by microorganisms is a promising technology to remove accumulated non-process elements in highly recycled biorefinery process water. Removal of these elements would enable greater water reuse and reduce the environmental impact of effluent discharge. A model lignocellulosic ethanol biorefinery wastewater was created based on pulp mill effluent. This generated a wastewater with an environmentally realistic high loading of dissolved natural organic matter (900?mg/l), a potentially important factor influencing metal biosorption. Analysis of feedstock and pulp mill effluent indicated that Mn and Zn are likely to be problematic in highly recycled lignocellulosic ethanol biorefinery process water. Therefore, the growth of several bacteria and fungi from existing collections, and some isolated from pulp mill effluent were tested in the model wastewater spiked with Mn and Zn (0.2?mM). Wastewater isolates grew the best in the wastewater. Metal uptake varied by species and was much greater for Zn than Mn. A bacterium, Novosphingobium nitrogenifigens Y88(T), removed the most metal per unit biomass, 35 and 17?mg?Mn/g. No other organism tested decreased the Mn concentration. A yeast, Candida tropicalis, produced the most biomass and removed the most total metal (38?% of Zn), while uptake per unit biomass was 24?mg?Zn/g. These results indicate that microorganisms can remove significant amounts of metals in wastewater with high concentrations of dissolved natural organic matter. Metal sorption by autochthonous microorganisms in an anaerobic bioreactor may be able to extend water reuse and therefore lower the water consumption of future biorefineries.     

The conformationally flexible S9-S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivo

Although the N-terminal BOX-I domain of the tumor suppressor protein p53 contains the primary docking site for MDM2, previous studies demonstrated that RNA stabilizes the MDM2.p53 complex using a p53 mutant lacking the BOX-I motif. In vitro assays measuring the specific activity of MDM2 in the ligand-free and RNA-bound state identified a novel MDM2 interaction site in the core domain of p53. As defined using phage-peptide display, the RNA.MDM2 isoform exhibited a notable switch in peptide binding specificity, with enhanced affinity for novel peptide sequences in either p53 or small nuclear ribonucleoprotein-U (snRNP-U) and substantially reduced affinity for the primary p53 binding site in the BOX-I domain. The consensus binding site for the RNA.MDM2 complex within p53 is SGXLLGESXF, which links the S9-S10 beta-sheets flanking the BOX-IV and BOX-V motifs in the core domain and which is a site of reversible conformational flexibility in p53. Mutation of conserved amino acids in the linker at Ser(261) and Leu(264), which bridges the S9-S10 beta-sheets, stimulated p53 activity from reporter templates and increased MDM2-dependent ubiquitination of p53. Furthermore, mutation of the conserved Phe(270) within the S10 beta-sheet resulted in a mutant p53, which binds more stably to RNA.MDM2 complexes in vitro and which is strikingly hyper-ubiquitinated in vivo. Introducing an Ala(19) mutation into the p53(F270A) protein abolished both RNA.MDM2 complex binding and hyper-ubiquitination in vivo, thus indicating that p53(F270A) protein hyper-ubiquitination depends upon MDM2 binding to its primary site in the BOX-I domain. Together, these data identify a novel MDM2 binding interface within the S9-S10 beta-sheet region of p53 that plays a regulatory role in modulating the rate of MDM2-dependent ubiquitination of p53 in cells.     

Legacy microsite effect on the survival of bitterbrush outplantings after prescribed fire: capitalizing on spatial variability to improve restoration

Restoration of shrubs in arid and semi‐arid rangelands is hampered by low success rates. Planting shrub seedlings is a method used to improve success in these rangelands; however, it is expensive and labor intensive. The efficiency of shrub restoration could be improved by identifying microsites where shrub survival is greater. Bitterbrush (Purshia tridentata Pursh DC) is an important shrub to wildlife that has declined because of conifer encroachment, excessive defoliation, wildfires, and low recruitment. We investigated planting bitterbrush seedlings in western juniper (Juniperus occidentalis ssp. occidentalis Hook) encroached shrublands after prescribed fire was used to control trees. Bitterbrush seedlings were planted in under (canopy) and between (interspace) former juniper canopies at five blocks and evaluated for three growing seasons. Bitterbrush survival was greater than 50% in the former canopy, but only 5% in the interspace microsite by the third growing season. Growth of bitterbrush was also greater in the former canopy compared with the interspace, potentially due to markedly less perennial vegetation in this microsite. Exotic annual grasses and annual forbs became prevalent in the former canopy in the second and third growing season, suggesting that soil resource availability was greater in this microsite. These results suggest that restoration success will vary by specific locations within a burned landscape and that this variability can be used to improve restoration efficiency. In this situation, bitterbrush restoration can be improved by planting seedlings in former canopy compared with interspace microsites.     

Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides

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PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of Mitochondrial Crista Junctions

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Deposition of pathogenic Mycoplasma gallisepticum onto bird feeders: host pathology is more important than temperature-driven increases in food intake

Although ambient temperature has diverse effects on disease dynamics, few studies have examined how temperature alters pathogen transmission by changing host physiology or behaviour. Here, we test whether reducing ambient temperature alters host foraging, pathology and the potential for fomite transmission of the bacterial pathogen Mycoplasma gallisepticum (MG), which causes seasonal outbreaks of severe conjunctivitis in house finches (Haemorhous mexicanus). We housed finches at temperatures within or below the thermoneutral zone to manipulate food intake by altering energetic requirements of thermoregulation. We predicted that pathogen deposition on bird feeders would increase with temperature-driven increases in food intake and with conjunctival pathology. As expected, housing birds below the thermoneutral zone increased food consumption. Despite this difference, pathogen deposition on feeders did not vary across temperature treatments. However, pathogen deposition increased with conjunctival pathology, independently of temperature and pathogen load, suggesting that MG could enhance its transmission by increasing virulence. Our results suggest that in this system, host physiological responses are more important for transmission potential than temperature-dependent alterations in feeding. Understanding such behavioural and physiological contributions to disease transmission is critical to linking individual responses to climate with population-level disease dynamics.     

The Effects of Incidentally Learned Temporal and Spatial Predictability on Response Times and Visual Fixations during Target Detection and Discrimination

Responses are quicker to predictable stimuli than if the time and place of appearance is uncertain. Studies that manipulate target predictability often involve overt cues to speed up response times. However, less is known about whether individuals will exhibit faster response times when target predictability is embedded within the inter-trial relationships. The current research examined the combined effects of spatial and temporal target predictability on reaction time (RT) and allocation of overt attention in a sustained attention task. Participants responded as quickly as possible to stimuli while their RT and eye movements were measured. Target temporal and spatial predictability were manipulated by altering the number of: 1) different time intervals between a response and the next target; and 2) possible spatial locations of the target. The effects of target predictability on target detection (Experiment 1) and target discrimination (Experiment 2) were tested. For both experiments, shorter RTs as target predictability increased across both space and time were found. In addition, the influences of spatial and temporal target predictability on RT and the overt allocation of attention were task dependent; suggesting that effective orienting of attention relies on both spatial and temporal predictability. These results indicate that stimulus predictability can be increased without overt cues and detected purely through inter-trial relationships over the course of repeated stimulus presentations.