CO2 Mitigation Potential of Plug-in Hybrid Electric Vehicles larger than expected.

The actual contribution of plug-in hybrid and battery electric vehicles (PHEV and BEV) to greenhouse gas mitigation depends on their real-world usage. Often BEV are seen as superior as they drive only electrically and do not have any direct emissions during driving. However, empirical evidence on which vehicle electrifies more mileage with a given battery capacity is lacking. Here, we present the first systematic overview of empirical findings on actual PHEV and BEV usage for the US and Germany. Contrary to common belief, PHEV with about 60 km of real-world range currently electrify as many annual vehicles kilometres as BEV with a much smaller battery. Accordingly, PHEV recharged from renewable electricity can highly contribute to green house gas mitigation in car transport. Including the higher CO2eq emissions during the production phase of BEV compared to PHEV, PHEV show today higher CO2eq savings then BEVs compared to conventional vehicles. However, for significant CO2eq improvements of PHEV and particularly of BEVs the decarbonisation of the electricity system should go on.

Structure characterization of unexpected covalent O-sulfonation and ion-pairing on an extremely hydrophilic peptide with CE-MS and FT-ICR-MS.

In this study, we characterized unexpected side-products in a commercially synthesized peptide with the sequence RPRTRLHTHRNR. This so-called peptide D3 was selected by mirror phage display against low molecular weight amyloid-ß-peptide (Aß) associated with Alzheimer's disease. Capillary electrophoresis (CE) was the method of choice for structure analysis because the extreme hydrophilicity of the peptide did not allow reversed-phase liquid chromatography (RPLC) and hydrophilic interaction stationary phases (HILIC). CE-MS analysis, applying a strongly acidic background electrolyte and different statically adsorbed capillary coatings, provided fast and efficient analysis and revealed that D3 unexpectedly showed strong ion-pairing with sulfuric acid. Moreover, covalent O-sulfonation at one or two threonine residues was identified as a result of a side reaction during peptide synthesis, and deamidation was found at either the asparagine residue or at the C-terminus. In total, more than 10 different species with different m/z values were observed. Tandem-MS analysis with collision induced dissociation (CID) using a CE-quadrupole-time-of-flight (QTOF) setup predominantly resulted in sulfate losses and did not yield any further characteristic fragment ions at high collision energies. Therefore, direct infusion Fourier transform ion cyclotron resonance (FT-ICR) MS was employed to identify the covalent modification and discriminate O-sulfonation from possible O-phosphorylation by using an accurate mass analysis. Electron transfer dissociation (ETD) was used for the identification of the threonine O-sulfation sites. In this work, it is shown that the combination of CE-MS and FT-ICR-MS with ETD fragmentation was essential for the full characterization of this extremely basic peptide with labile modifications.

Amyloid aggregation inhibitory mechanism of arginine-rich D-peptides.

It is widely believed that Alzheimer's disease pathogenesis is driven by the production and deposition of the amyloid-ß peptide (Aß) in the brain. In this study, we employ a combination of in silico and in vitro approaches to investigate the inhibitory properties of selected arginine-rich D-enantiomeric peptides (D-peptides) against amyloid aggregation. The D-peptides include D3, a 12-residue peptide with anti-amyloid potencies demonstrated in vitro and in vivo, RD2, a scrambled sequence of D3, as well as truncated RD2 variants. Using a global optimization method together with binding free energy calculations followed by molecular dynamics simulations, we perform a detailed analysis of D-peptide binding to Aß monomer and a fibrillar Aß structure. Results obtained from both molecular simulations and surface plasmon resonance experiments reveal a strong binding of D3 and RD2 to Aß, leading to a significant reduction in the amount of ß structures in both monomer and fibril, which was also demonstrated in Thioflavin T assays. The binding of the D-peptides to Aß is driven by electrostatic interactions, mostly involving the D-arginine residues and Glu11, Glu22 and Asp23 of Aß. Furthermore, we show that the anti-amyloid activities of the D-peptides depend on the length and sequence of the Dpeptide, its ability to form multiple weak hydrophobic interactions with Aß, as well as the Aß oligomer size.

Detection of α-synuclein aggregates by fluorescence microscopy.

Parkinson disease (PD) is one of the most common age-related neurodegenerative diseases associated with motor deficiencies in humans. The symptoms are caused by the death of dopaminergic neurons in the brain, which is accompanied by the misfolding and aggregation of the protein α-synuclein. Diagnosis is based on the incidence of clinical symptoms, although they only appear as a result of the irreversible damage of neurons during the disease. Identification of a suitable biomarker would allow preclinical diagnosis. We an approach to quantify single α-synuclein aggregates as a possible biomarker for PD.

A survey of peptides with effective therapeutic potential in Alzheimer's disease rodent models or in human clinical studies.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia. Today, only palliative therapies are available. The pathological hallmarks of AD are the presence of neurofibrillary tangles and amyloid plaques, mainly composed of the amyloid-ß peptide (Aß), in the brains of the patients. Several lines of evidence suggest that the increased production and/or decreased cleavage of Aß and subsequent accumulation of Aß oligomers and aggregates play a fundamental role in the disease progress. Therefore, substances which bind to Aß and influence aggregation thereof are of great interest. A wide range of Aß binding peptides were investigated to date for therapeutic purposes. Only very few were shown to be effective in rodent AD models or in clinical studies. Here, we review those peptides and discuss their possible mechanisms of action.

Detection of Amyloid-beta aggregates in body fluids: a suitable method for early diagnosis of Alzheimer's disease?

Today, the most reliable diagnosis for Alzheimer's disease (AD) is the post mortem identification of amyloid plaques, consisting of the Amyloid-beta (Abeta) peptide, (and neurofibrillary tangles) in the brain of the patient. Great efforts are being made to identify reliable biomarkers for AD that are suitable for minimal invasive early diagnosis and prognosis of AD. During the past years, body fluids of AD patients were assayed for their content of total or soluble Abeta(1-40) or Abeta(1-42) concentrations using classical (ELISA) or non-classical (with additional signal amplification) read-out. Cerebrospinal fluid (CSF) concentrations of soluble Abeta(1-42) are reduced by 40 to 50 % in AD patients compared to age-matched healthy controls as confirmed in more than 30 studies, with both sensitivity and specificity exceeding 80 % in most of the studies. Thus, it was suggested that low levels of CSF Abeta(1-42) might be useful for preclinical diagnosis. Because the current average sensitivity of AD biomarker detection in the CSF is approximately 85 %, these assays do not offer a considerable increase in predictive value over existing algorithms based on neuropsychological and imaging modalities. Regarding the amyloid cascade hypothesis, Abeta oligomers and aggregates are directly involved in the pathogenic process. Therefore, presence of Abeta aggregates seem to be the most direct disease biomarker for AD and increasing effort is being made into the development of methods suitable for the detection of different Abeta aggregates in body fluids like CSF and plasma. We therefore give an overview of the current state of Abeta aggregate specific detection.