Modelling phosphorus fluxes in Loweswater

1. This is the final report to the Loweswater Care Project (in support of the Catchment Restoration Fund for England) ECRC-ENSIS Project 298, 'Loweswater 12-13'. The study was concerned with the spatial and temporal concentrations of sediment phosphorus (P) in the lake and the use of P measurements from the water column and inflow and outflow samples to derive a simple mass balance model for P in the lake. 2. A review of published and unpublished literature on Loweswater highlighted trends in water chemistry since the mid-eighteenth century. Land use and farming practises have changed over the past 200 years which have led to increased nutrient loading to the lake with significant increases occurring in the mid part of the last century. Agricultural intensification is likely to be a significant cause of the problem as well as inadequate septic tank management. Local management efforts, led by the Loweswater Care Project, has sought to reduce the primary sources of nutrients reaching the lake, but total phosphorus (TP) concentrations in the lake remain higher than desired. 3. Temperature and dissolved oxygen (DO) profiling confirmed that the site stratified in summer with major changes in DO occurring below a depth of 8 m. The deeper waters were almost entirely anoxic. During stratification the maximum TP value was recorded at the lake bottom. This is a clear indication that P is being released from the lake bed during summer stratification. 4. Analysis of the stream water from the Dub Beck inflow (data for 2013), shows that P influx remains high enough to explain the elevated lake water P concentrations, despite considerable efforts to reduce catchment P sources. 5. Analysis of the water column P profiles shows that P release from the sediment is only a minor contribution to the P load. While the sediment core data reveals a substantial pool of P in the sediment very little of this should be released each year to the water column. In 2013 it is estimated that more than 90% of the P came from the catchment and only ~10% from the sediment. 6. As with all modelling exercises there are uncertainties inherent in the approach. In this case the model output is based on a single year of input data for the inflow P flux calculations and it would be preferable to have a longer data series to inform the modelling. Inflow fluxes are highly dependent on flow conditions and here, in the absence of flow data from Dub Beck, we used data from a nearby stream. Further, the monthly sampling has resulted in most samples being taken in low flow conditions, thus missing potential storm flow conditions. Finally, stream input information is restricted to Dub Beck, and contributions from the other stream is unknown. 7. Nevertheless, the results from the modelling are clear and on that basis we conclude that the priority is for P loading to the lake to be reduced by better catchment management and that lake manipulation is not warranted. Integrated catchment management supported by modelling together with local stakeholder engagement should provide the most effective means of improving the condition of the lake

NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses

Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.Kendall W Nettles, John B Bruning, German Gil, Jason Nowak, Sanjay K Sharma, Johnnie B Hahm, Kristen Kulp, Richard B Hochberg, Haibing Zhou, John A Katzenellenbogen, Benita S Katzenellenbogen, Younchang Kim, Andrzej Joachimiak & Geoffrey L Green

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine-via α2β2-containing nicotinic receptors-to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.peerReviewe