Search

Engineered UCNP are used to trigger rapid photoconversion of the fluorescent protein Dendra2 with nanoscopic precision and over longer distances in mammalian cells. By exploiting the synergy of high-level thulium doping with core-shell design and elevated excitation intensities, intense UCNP emission is achieved, allowing fast photoconversion of Dendra2 with <10 nm resolution. A tailored biocompatible surface coating and functionalization with a derivate of green fluorescent protein (GFP) for recognition of antiGFP nanobodies are developed. Highly specific targeting of UCNP to fusion proteins of antiGFP on the surface of mammalian cells is demonstrated. UCNP bound to extracellular Dendra2 enable rapid photoconversion selectively in molecular proximity and thus unambiguous detection of cytokine receptor dimerization in the plasma membrane and in endosomes. Remarkably, UCNPs are also suited for manipulating intracellular Dendra2 across the plasma membrane. This study thus establishes UCNP-controlled photomanipulation with nanoscale precision, opening exciting opportunities for bioanalytical applications in cell biology.

Ongoing acidification of the ocean through uptake of anthropogenic CO2 is known to affect marine biota and ecosystems with largely unknown consequences for marine food webs. Changes in food web structure have the potential to alter trophic transfer, partitioning, and biogeochemical cycling of elements in the ocean. Here we investigated the impact of realistic end-of-the-century CO2 concentrations on the development and partitioning of the carbon, nitrogen, phosphorus, and silica pools in a coastal pelagic ecosystem (Gullmar Fjord, Sweden). We covered the entire winter-to-summer plankton succession (100 days) in two sets of five pelagic mesocosms, with one set being CO2 enriched (~760 μatm pCO2) and the other one left at ambient CO2 concentrations. Elemental mass balances were calculated and we highlight important challenges and uncertainties we have faced in the closed mesocosm system. Our key observations under high CO2 were: (1) A significantly amplified transfer of carbon, nitrogen, and phosphorus from primary producers to higher trophic levels, during times of regenerated primary production. (2) A prolonged retention of all three elements in the pelagic food web that significantly reduced nitrogen and phosphorus sedimentation by about 11 and 9%, respectively. (3) A positive trend in carbon fixation (relative to nitrogen) that appeared in the particulate matter pool as well as the downward particle flux. This excess carbon counteracted a potential reduction in carbon sedimentation that could have been expected from patterns of nitrogen and phosphorus fluxes. Our findings highlight the potential for ocean acidification to alter partitioning and cycling of carbon and nutrients in the surface ocean but also show that impacts are temporarily variable and likely depending upon the structure of the plankton food web., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Adequate volume management removing excess volume and at the same time avoiding intradialytic morbid events (IME) remains a core problem in current hemodialysis (HD) therapy. Recently, we developed a feasible method to determine absolute blood volume (Vs, in mL/kg) in patients on HD. The aim of this study was to investigate the suitability of Vs measurements for volume management., Methods: Following a 4 week baseline phase to quantify the frequency of IME, volume status was determined in a single specified HD session during which Vs was measured using dialysate dilution, volume overload (Vo, L) was measured using bioimpedance spectroscopy, and the occurrence of IME was recorded. Target weight was then adjusted and the frequency of IME was recorded during 4 weeks of follow-up., Findings: Forty-five patients participated in this study. Twenty-two (49%) patients experienced 66 IME in 12% of HD treatments during baseline. In 15 (33%) patients who experienced IME during volume assessment both Vs (60.7 ± 4.0 vs. 73.7 ± 11.3 mL/kg, P < 0.001) and Vo (1.1 ± 0.9 vs. 2.5 ± 1.8 L, P < 0.01) were significantly lower than in stable patients, respectively. The sensitivity, specificity, and accuracy of the ≤65 mL/kg Vs threshold to predict IME was 87%, 100%, and 91%, respectively. Target weight was increased (+1.5 kg) or decreased (-5 kg) in 32 patients. The frequency of IME fell to 0.9% of all HD sessions in the following 4 weeks (P < 0.001)., Discussion: Adjustment of target weight based on information of Vs, Vo, and IME appears as a feasible approach to reduce the frequency of IME., (© 2017 International Society for Hemodialysis.)

Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (~380 μatm pCO2), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (~760 μatm pCO2). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.

The reduction of blood volume below a critical threshold is assumed to trigger intradialytic morbid events (IME). Recently, we presented a simple method to determine the absolute blood volume during routine hemodialysis (HD) carried out without blood sampling and without injection of dyes or radiolabeled markers. Such information could be used to detect excessive volume reduction during HD and to prevent IME. Therefore, we performed a pilot study in IME-prone patients to identify the absolute blood volume at which they developed clinical symptoms. A volume of 240 mL of ultrapure dialysate was automatically infused into the extracorporeal circulation using the bolus function of a commercial online hemodiafiltration machine incorporating a blood volume monitor (BVM). The increase in relative blood volume (RBV) caused by the infusion was measured and used to determine the absolute blood volume at that time. The blood volume per kilogram body mass at the time of symptomatic IME was also determined. All IME-prone patients of a single-dialysis center were included in the study. Ten out of 12 patients became symptomatic at a specific blood volume between 65 and 56 mL/kg (mean 62 mL/kg) whereas RBV showed a wide scatter (82-97%). A specific blood volume of 65 mL/kg seems to represent the threshold for IME by this method. The technique could be completely automated without altering the hardware of the dialysis device. Present feedback systems for automated blood volume-controlled ultrafiltration could be adapted to maintain absolute blood volume above this critical volume to safely prevent volume-dependent IME., (© 2015 International Society for Hemodialysis.)

Background: In Germany, every fifth patient starting dialysis is now 80 years of age or older. The question that is currently relevant is not whether we have to treat patients who are older than 80. Rather the question now is how to treat this elderly group of patients., Methods: Single centre data of all dialysis patients aged over 80 were analyzed with regard to survival, social circumstances, vascular access, and pre-dialysis nephrology care., Results: Between 2001 and 2012, 76 patients over 80 years started chronic ambulatory hemodialysis treatment. One-year survival was 87%, 3-year survival 52%, 5-year survival 27% and 10-year survival 9%. Patients (n = 55) with more than 3 months of nephrological care prior to dialysis (3-161 months, median 31 months) survived significantly longer then patients (n = 21) having had less than 3 months contact with nephrologists. On 31st December 2012 there were 38 patients aged ≥80 (median age 84, 80-95 years) in the chronic hemodialysis program accounting for 19% of all dialysis patients of this center. Thirty patients (79%) had been in long-term nephrological care prior to dialysis initiation (3-161 months, median 45 months). Thirty one patients (82%) started the first dialysis treatment with a functioning shunt access., Conclusion: Long-term pre-dialysis nephrology care is of most importance for successful dialysis treatment in the elderly, especially in octogenarians and nonagenarians. It enables the early establishment of functioning vascular access and careful scheduling of first dialysis treatment and increases survival. The long-term use of catheters can be avoided in almost all patients above the age of 80. © 2015 S. Karger AG, Basel.

Facial tremor occurring on smiling is a rare phenomenon and has been described (to the best of our knowledge) in the literature only once. We describe two patients who presented with a bilateral facial tremor that occurred only on smiling and other activation of therisorii muscles and had a high frequency of 9 Hz. One patient additionally suffered from young-onset Parkinson's disease, whereas the other had no further neurological symptoms or signs apart from this tremor. Anti-parkinsonian medication was unhelpful for the facial tremor in the patient with Parkinson's disease. Tremor on smiling may be a discrete entity or may be associated in some cases of Parkinson's disease., (Copyright 2009 Movement Disorder Society.)

The aim of this study was to investigate which antihormonal treatment strategies are used in German forensic psychiatric institutions. Forensic clinics were asked about the number of treated patients. Four hundred seventy-four patients were committed for sex offences; 12% received either CPA (n = 29) or LHRH- agonists (n = 29). Differences in efficacy were small. Several side effects confirm the importance of a protocol for minimizing medical complications.