Decadal changes in water temperature and ecological time-series in Lake Geneva, Europe - detecting relationships with the subtropical Atlantic climate variability

We investigated connections between subtropical Atlantic climate variability, atmospheric conditions in the European Alpine region (45 to 47° N and 5 to 8° E) and the interannual variability of the thermal conditions in the largest body of freshwater in Western Europe (Lake Geneva). The long-term water temperature was related to climate variability by means of a multivariate regression model. Results revealed atmospheric connections that have been elusive so far, and showed that over the period from 1959 to 2000, summer thermal conditions in Lake Geneva appear tightly linked to the long-term variability of the subtropical Atlantic climate. The multivariate model revealed high skills and tight correlations, which suggest the possibility of assessing future thermal changes in Lake Geneva from the Atlantic climate variability. The implications of such climatic forcing on the functioning of the pelagic ecosystem in Lake Geneva were illustrated by analysing the long-term changes in abundance of the summer-dominant carnivorous cladocerans Bythotrephes longimanus and Leptodora kindtii during the period 1974 to 2000. Again, the multivariate model revealed high skills and excellent correlations between the interannual changes in abundance of these species and the variability of summer climate. Our approach provides a general understanding of the interrelations between large- and regional-scale climates, local environmental conditions and the ecological responses in Lake Geneva during summer, and is therefore applicable to other retrospective studies

Neuropathic complications after 157 procedures of continuous popliteal nerve block for hallux valgus surgery. A retrospective study

SummaryBackgroundContinuous peripheral nerve block (CPNB), in particular at the popliteal fossa, is widely used in orthopedic surgery, allowing good postoperative analgesia. Possible neuropathic complications, however, remain poorly known.ObjectiveTo review the characteristics of peripheral neuropathy (PN) after sciatic CPNB at the popliteal fossa, estimating prevalence, severity, evolution and possible risk factors, especially those relating to the procedure.MethodsRetrospective study of PN associated with popliteal fossa CPNB for hallux valgus surgery, between November 1st, 2005 and November 1st, 2009. All procedures were analyzed (type of anesthesia, approach, nerve location technique, number of procedures by operator) with, for each case of PN, analysis of clinical and electromyographic data.ResultsOne hundred and fifty seven sciatic CPNBs were performed (92% women; mean age, 55 years). The approach was lateral (n=62), posterior (n=74) or unknown (n=21). Ultrasound guidance was combined to neurostimulation for 69 patients (44%). Three women (prevalence=1.91%), aged 19, 24 and 65 years respectively, developed associated common superficial peroneal and sural nerve injury (2), axonal on electromyography, with motor (n=1) and/or sensory (n=3) residual dysfunction.DiscussionThe higher prevalence found in the present study than in the literature (0 to 0.5%) raises questions of methodological bias or technical problems. The common peroneal and sural nerves seem to be exposed, unlike the tibial. Several mechanisms can be suggested: anesthetic neurotoxicity, direct mechanical lesion, or tourniquet-related ischemia and conduction block. Further studies are necessary to determine the ideal anesthetic procedure.ConclusionPatients should be informed of the potential risk, however rare, even during mild surgery. The best possible technique should be implemented, with reinforced surveillance.Level of evidenceLevel IV retrospective study

Bis(2,3,5,6-tetra-2-pyridylpyrazine-κ3 N 2,N 1,N 6)iron(II) bis­(dicyanamidate) 4.5-hydrate

In the title compound, [Fe(C24H16N6)2][N(CN)2]2·4.5H2O, the central iron(II) ion is hexa­coordinated by six N atoms of two tridentate 2,3,5,6-tetra-2-pyridylpyrazine (tppz) ligands. Two dicyanamide anions [dca or N(CN)2 −] act as counter-ions, and 4.5 water mol­ecules act as solvation agents. The structure contains isolated cationic iron(II)–tppz complexes and the final neutrality is obtained with the two dicyanamide anions. One of the dicyanamide anions and a water mol­ecule are disordered with an occupancy ratio of 0.614 (8):0.386 (8). O—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds involving dca, water and tppz mol­ecules are observed

Stereospecific Lasofoxifene Derivatives Reveal the Interplay between Estrogen Receptor Alpha Stability and Antagonistic Activity in <i>ESR1</i> Mutant Breast Cancer Cells

Chemical manipulation of estrogen receptor alpha ligand binding domain structural mobility tunes receptor lifetime and influences breast cancer therapeutic activities. Selective estrogen receptor modulators (SERMs) extend ERα cellular lifetime/accumulation. They are antagonists in the breast but agonists in the uterine epithelium and/or in bone. Selective estrogen receptor degraders/downregulators (SERDs) reduce ERα cellular lifetime/accumulation and are pure antagonists. Activating somatic ESR1 mutations Y537S and D538G enable resistance to first-line endocrine therapies. SERDs have shown significant activities in ESR1 mutant setting while few SERMs have been studied. To understand whether chemical manipulation of ERα cellular lifetime and accumulation influences antagonistic activity, we studied a series of methylpyrollidine lasofoxifene derivatives that maintained the drug’s antagonistic activities while uniquely tuning ERα cellular accumulation. These molecules were examined alongside a panel of antiestrogens in live cell assays of ERα cellular accumulation, lifetime, SUMOylation, and transcriptional antagonism. High-resolution x-ray crystal structures of WT and Y537S ERα ligand binding domain in complex with the methylated lasofoxifene derivatives or representative SERMs and SERDs show that molecules that favor a highly buried helix 12 antagonist conformation achieve the greatest transcriptional suppression activities in breast cancer cells harboring WT/Y537S ESR1. Together these results show that chemical reduction of ERα cellular lifetime is not necessarily the most crucial parameter for transcriptional antagonism in ESR1 mutated breast cancer cells. Importantly, our studies show how small chemical differences within a scaffold series can provide compounds with similar antagonistic activities, but with greatly different effects of the cellular lifetime of the ERα, which is crucial for achieving desired SERM or SERD profiles. SIGNIFICANCE This study shows that antiestrogens that enforce a wild-type-like estrogen receptor alpha antagonist conformation demonstrate improved therapeutic activities in hormone-resistant breast cancer cells harboring activating Y537S ESR1 mutant

Root growth and nitrate uptake of three different catch crops in deep soil layers

Catch crops can reduce NO3 losses from leaching, but little is known about the importance of deep rooting for the efficiency of NO3 depletion. In a field experiment, we investigated the N uptake and root growth of three types of catch crops using minirhizotrons (glass tubes of 70-mm o.d.) reaching 2.4 m. Our purpose was to evaluate minirhizotron methodology and the importance of deep rooting in the ability of catch crops to take up NO3 from deep soil layers. Nitrogen uptake was studied over a 6-d period at the end of October by injection of 15NO3 at four depths in the ranges: 0.4 to 1, 0.5 to 1.4, and 1 to 2.5 m under Italian ryegrass (Lolium multiflorum Lam.), winter rye (Secale cereale L.), and fodder radish (Raphanus sativus L. var. oleiformis Pers.), respectively. The root depth of the three species were 0.6, 1.1, and more than 2.4 m, respectively. No 15N was taken up from placements below root depth, and linear relationships were found between root density and 15N uptake from different depths. Residual soil NO3 of 18, 59, and 87 kg N ha−1 was left under fodder radish, winter rye, and ryegrass, respectively. The measurements obtained with the minirhizotron method were highly relevant for evaluating N uptake from different soil layers, and root depths of the catch crops were important for N depletion. Knowledge about root growth and N uptake in deep soil layers may be utilized when designing crop rotations with improved N use efficiency. Where N has been left by a preceding crop and leached to deeper soil layers, it may be recycled by deep-rooted catch crops

Inhibition of ectopic glioma tumor growth by a potent ferrocenyl drug loaded into stealth lipid nanocapsules.

UNLABELLED: In this work, a novel ferrocenyl complex (ansa-FcdiOH) was assessed for brain tumor therapy through stealth lipid nanocapsules (LNCs). Stealth LNCs, prepared according to a one-step process, showed rapid uptake by cancer cells and extended blood circulation time. The ferrocenyl complex was successfully encapsulated into these LNCs measuring 40nm with a high loading capacity (6.4%). In vitro studies showed a potent anticancer effect of ansa-FcdiOH on 9L cells with a low IC50 value (0.1μM) associated with an oxidative stress and a dose-dependent alteration of the cell cycle. Repeated intravenous injections of stealth ansa-FcdiOH LNCs in ectopic glioma bearing rats induced a significant tumor growth inhibition, supported by a reduced number of proliferative cells in tumors compared to control group. Additionally, no liver damage was observed in treated animals. These results indicated that stealth ansa-FcdiOH LNCs might be considered as a potential new approach for cancer chemotherapy. FROM THE CLINICAL EDITOR: In this study, a novel ferrocenyl complex was assessed for brain tumor therapy through stealth lipid nanocapsules, demonstrating no liver damage, and superior tumor volume reduction compared to saline and stealth lipid nanocapsules alone in an ectopic glioma model

Position and motions of the S4 helix during opening of the Shaker potassium channel

The four voltage sensors in voltage-gated potassium (Kv) channels activate upon membrane depolarization and open the pore. The location and motion of the voltage-sensing S4 helix during the early activation steps and the final opening transition are unresolved. We studied Zn2+ bridges between two introduced His residues in Shaker Kv channels: one in the R1 position at the outer end of the S4 helix (R362H), and another in the S5 helix of the pore domain (A419H or F416H). Zn2+ bridges readily form between R362H and A419H in open channels after the S4 helix has undergone its final motion. In contrast, a distinct bridge forms between R362H and F416H after early S4 activation, but before the final S4 motion. Both bridges form rapidly, providing constraints on the average position of S4 relative to the pore. These results demonstrate that the outer ends of S4 and S5 remain in close proximity during the final opening transition, with the S4 helix translating a significant distance normal to the membrane plane

An impact assessment for urban stormwater use

The adoption of stormwater collection and use for a range of non-potable applications requires that the perceived risks, particularly those associated with public health, are addressed. Pollutant impacts have been assessed using E. coli and a scoring system on a scale of 0 to 5 to identify the magnitude of impacts and also the likelihood of exposure to stormwater during different applications. Combining these identifies that low or medium risks are generally predicted except for domestic car washing and occupational irrigation of edible raw food crops where the predicted high risk would necessitate the introduction of remedial action