CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection

Thermal High Performance Storages for use in vehicle applications

To overcome the restrictions on electric vehicles ranges on winter term conditions, due to the heating demand of the interior, the use of a Thermal High Performance Storage with metallic Phase Change Materials is one possible solution. A new storage concept, using a so called Heat Transport System, enabling the heat transfer from the storage to a vehicles cooling fluid by evaporation and condensation of a working fluid within a closed circle, is introduced in this study. The influence of the storage on an electric vehicles range is exemplary shown for DLR´s Urban Modular Vehicle Concept for a motorway cycle by theoretical investigations. An increase of range by 36,3 km resp. 18,4 % for an ambient temperature of -10 °C and 46 km resp. 26,7 % for an ambient temperature of -20 °C could be reached. The energy densities of the designed storages reach values of more than 220 Wh/kg resp. more than 310 Wh/l. The cost estimations for those storage systems are approx. 445 € resp. 660 €. A comparison between the thermal energy storage and a conventional heating system consisting out of a PTC-Heater and a battery show, that the conventional heating system has a mass which is about two thirds higher, a volume which is more than one third higher and a quadrupled price compared to the thermal energy storage

Asymmetry of Discharge/Charge Curves of Lithium-Ion Battery Intercalation Electrodes

Nickel cobalt aluminum oxide (NCA) based lithium-ion battery electrodes exhibit a distinct asymmetry in discharge/charge behavior towards high bulk stoichiometry (low state of charge). We show that basic electrochemical relationships, that is, the Nernst equation and the Butler-Volmer equation, are able to reproduce this behavior when a two-step reaction mechanism is assumed. The two-step mechanism consists of (1) lithium-ion adsorption from the electrolyte onto the active material particle surface under electron transfer, and (2) intercalation of surface-adsorbed lithium atoms into the bulk material. The asymmetry of experimental half-cell data of an NCA electrode cycled at 0.1 C-rate can be quantitatively reproduced with this simple model. The model parameters show two alternative solutions, predicting either a saturated (highly-covered) or a depleted surface for high bulk lithiation

Pilot study of an Alzheimer's disease risk assessment program in a primary care setting.

IntroductionThe goal of this study was to pilot a referral-based cognitive screening and genetic testing program for Alzheimer's disease (AD) risk assessment in a primary care setting.MethodsPrimary care providers (PCPs; N = 6) referred patients (N = 94; M = 63 years) to the Rhode Island Alzheimer's Disease Prevention Registry for apolipoprotein E (APOE) genotyping and cognitive screening. PCPs disclosed test results to patients and counseled them about risk factor modification.ResultsCompared to the Registry as a whole, participants were younger, more likely to be non-White, and had lower cognitive screening scores. Mild cognitive impairment participants correctly reported a higher perceived risk of developing AD. Patients who recalled being counseled about modifiable risk factors were more likely to report positive health behavior changes.DiscussionA referral-based program for cognitive and genetic AD risk assessment in a primary care setting is feasible, acceptable to patients, and yielded a more demographically diverse sample than an AD prevention registry

No association between APOE genotype and lipid lowering with cognitive function in a randomized controlled trial of evolocumab

APOE encodes a cholesterol transporter, and the ε4 allele is associated with higher circulating cholesterol levels, ß-amyloid burden, and risk of Alzheimer’s disease. Prior studies demonstrated no significant differences in objective or subjective cognitive function for patients receiving the PCSK9 inhibitor evolocumab vs. placebo added to statin therapy. There is some evidence that cholesterol-lowering medications may confer greater cognitive benefits in APOE ε4 carriers. Thus, the purpose of this study was to determine whether APOE genotype moderates the relationships between evolocumab use and cognitive function. APOE -genotyped patients (N = 13,481; 28% ε4 carriers) from FOURIER, a randomized, placebo-controlled trial of evolocumab added to statin therapy in patients with stable atherosclerotic cardiovascular disease followed for a median of 2.2 years, completed the Everyday Cognition Scale (ECog) to self-report cognitive changes from the end of the trial compared to its beginning; a subset (N = 835) underwent objective cognitive testing using the Cambridge Neuropsychological Test Automated Battery as part of the EBBINGHAUS trial. There was a dose-dependent relationship between APOE ε4 genotype and patient-reported memory decline on the ECog in the placebo arm ( p = .003 for trend across genotypes; ε4/ε4 carriers vs. non-carriers: OR = 1.46, 95% CI [1.03, 2.08]) but not in the evolocumab arm ( p = .50, OR = 1.18, 95% CI [.83,1.66]). However, the genotype by treatment interaction was not significant ( p = .30). In the subset of participants who underwent objective cognitive testing with the CANTAB, APOE genotype did not significantly modify the relationship between treatment arm and CANTAB performance after adjustment for demographic and medical covariates, ( p ’s>.05). Although analyses were limited by the low population frequency of the ε4/ε4 genotype, this supports the cognitive safety of evolocumab among ε4 carriers, guiding future research on possible benefits of cholesterol-lowering medications in people at genetic risk for Alzheimer’s disease