Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

There is a need for a blood biomarker of disease activity in ALS. This marker needs to measure the loss of motor neurones. Phosphorylated neurofilament heavy chain (pNfH) in the serum is a biomarker of axonal injury. Previous studies have found that levels of pNfH are elevated in ALS. We have performed a serial study of pNfH levels in 98 subjects from our ALS clinic. There was significant elevation of levels of pNfH in subjects with ALS compared to controls, although there was considerable variability. In studies of individuals who had two or more serial samples, we found that the levels of pNfH increased over time in the early stage of disease. Levels were low in subjects with long survival. The rate of rise of pNfH was inversely correlated with survival. We suggest that the initial level of pNfH is a marker of disease severity and that changes in pNfH levels are markers of disease progression

Decreased T cell reactivity to Epstein–Barr virus infected lymphoblastoid cell lines in multiple sclerosis

Objective: To investigate T cell and antibody immunity to Epstein-Barr virus (EBV) in multiple sclerosis (MS)

Platelet inhibitors versus anticoagulants for prevention of aorto-coronary bypass graft occlusion

The effects of the antiaggregant substance ticlopidine and of the anticoagulant acenocoumarol on patency rates of aorto-coronary bypass grafts were compared in a prospective randomized trial. Ticlopidine, 250 mg b.i.d. was administered orally from the first postoperative day till angiography, while anticoagulation with acenocoumarol was initiated on the second to third postoperative day. Side-effects of ticlopidine were rare and patient management with the standard dosage of this drug was easier than oral anticoagulation. From an initial group of 166 randomized patients 149 completed the trial by coronary angiography three months postoperatively. The 78 patients in the ticlopidine group showed a compliance of 85%. The average prothrombin time in the 71 patients receiving acenocoumarol was 26.9%. Detailed statistical analysis of the two study groups revealed no reason to doubt the correctness of randomization. Coronary angiography showed an average patency rate per patient of 84% with ticlopidine and of 82% with acenocoumarol. This and various other measures of graft occlusion did not reveal any substantial difference in graft patency of patients receiving ticlopidine or acenocoumarol. It is concluded that ticlopidine may well be used instead of anticoagulants forprevention of postoperative occlusion of aorto-coronary bypass graft

The role of hydrogen in a greenhouse gas-neutral energy supply system in Germany

Hydrogen is widely considered to play a pivotal role in successfully transforming the German energy system, but the German government\u27s current “National Hydrogen Strategy” does not specify how hydrogen utilization, production, storage or distribution will be implemented. Addressing key uncertainties for the German energy system\u27s path to greenhouse gas-neutrality, this paper examines hydrogen in different scenarios. This analysis aims to support the concretization of the German hydrogen strategy. Applying a European energy supply model with strong interactions between the conversion sector and the hydrogen system, the analysis focuses on the requirements for geological hydrogen storages and their utilization over the course of a year, the positioning of electrolyzers within Germany, and the contributions of hydrogen transport networks to balancing supply and demand. Regarding seasonal hydrogen storages, the results show that hydrogen storage facilities in the range of 42 TWhH2 to 104 TWhH2 are beneficial to shift high electricity generation volumes from onshore wind in spring and fall to winter periods with lower renewable supply and increased electricity and heat demands. In 2050, the scenario results show electrolyzer capacities between 41 GWel and 75 GWel in Germany. Electrolyzer sites were found to follow the low-cost renewable energy potential and are concentrated on the North Sea and Baltic Sea coasts with their high wind yields. With respect to a hydrogen transport infrastructure, there were two robust findings: One, a domestic German hydrogen transport network connecting electrolytic hydrogen production sites in northern Germany with hydrogen demand hubs in western and southern Germany is economically efficient. Two, connecting Germany to a European hydrogen transport network with interconnection capacities between 18 GWH2 and 58 GWH2 is cost-efficient to meet Germany\u27s substantial hydrogen demand

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

The GOAT-Ghrelin System Is Not Essential for Hypoglycemia Prevention during Prolonged Calorie Restriction

Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation. Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum chow intake). Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin. Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes. The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction

Ion-selective electrode biochip for applications in a liquid environment

Physiological sensing conducted in a liquid environment requires electrodes with long lifetime. The development of a robust ion-selective electrode–based biochip in a lab-on-a-chip platform is described. To compare electrode lifetime, which is driven by the transducer layer, electrochemical measurements were performed in a custom-made flow-cell chamber. The results of potentiometric measurement of cationic analytes demonstrate the electrodes to have a near-Nernstian slope profile even after they are stored for almost a month in liquid medium. The electrodes also achieved H2O2 amperometric sensitivity (1.25 and 3.32 µAmM-1cm-2 for PEDOT:PSS and PEDOT:CaSO4 respectively) and lower detection limit (2.21 µM, 8.4 µM, 3.44 µM, for H+, NH4+, Ca2+ respectively) comparable to that of wire-type electrodes. Furthermore, the lifetime is dependent on the electrodeposition method of the conductive polymer, and the transducer layer must be modified to fit the analyte types. These results indicate that extended lifetime of microfabricated ion-selective electrodes in a multiplex format can be realized by optimizing the microfabricated electrode surface functionalization