HRSC Mapping Database: A New Tool to Collect and View Available HRSC-Based Geological Maps Worldwide

We present a new online database for quick and easy access to already published HRSC-based geological mappings on Mars

Comparison of urinary monitoring, faecal monitoring and erythrocyte analysis of stable isotope labels to determine magnesium absorption in human subjects

We have evaluated urinary monitoring and erythrocyte analysis to determine Mg absorption in human subjects as alternatives to the conventional technique of faecal monitoring by stable-isotope techniques. Ten healthy adults received 2·2 mmol 25Mg in water, together with wheat bread, followed 15 min later by intravenous injection of 0·6 mmol 26Mg (day 1). Brilliant blue and Yb (given on day 0 and day 1 respectively) served as qualitative and quantitative faecal markers. Urine was collected for 6 d after test meal intake. Complete collections of faeces were made until excretion of the second brilliant blue marker (given on day 7). Mg isotope ratios were determined by thermal ionisation-MS in urine and faeces and by inductively coupled plasma-MS in erythrocytes. Absorption was determined based on: (1) 6 d urine pools; (2) 24 h urine pools (collected 22-46 h after test meal intake); (3) erythrocytes from a blood sample drawn on day 14; (4) complete 6 d faecal pools; (5) faecal pools based on the first three consecutive stools after excretion of the first brilliant blue marker. Differences in mean Mg absorption (42 44 %) were statistically insignificant between techniques, except when based on 6 d urine pools for which the value was significantly lower (33 (sd 7) %, P=0·0003, ANOVA). The results indicate that Mg absorption can be determined from 24 h urine pools or erythrocytes obtained 14 d after test meal intake, an alternative method to the more time-consuming and labour-intense faecal monitoring. The choice of technique depends on practical and financial consideration

Industrial application of all oxide ceramic matrix composites

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PMCA for Ultrasensitive Detection of Prions and To Study Disease Biology

The emergence of a novel class of infectious agent composed exclusively of a misfolded protein (termed prions) has been a challenge in modern biomedicine. Despite similarities on the behavior of prions with respect to conventional pathogens, the many uncertainties regarding the biology and virulence of prions make them a worrisome paradigm. Since prions do not contain nucleic acids and rely on a very different way of replication and spreading, it was necessary to invent a novel technology to study them. In this article, we provide an overview of such a technology, termed protein misfolding cyclic amplification (PMCA), and summarize its many applications to detect prions and understand prion biology

Russland beendet die vorläufige Anwendung des Energiecharta-Vertrages

Russland verlässt den Energiechartaprozess. Am 30. Juli 2009 verfügte die russische Regierung – von der westlichen Öffentlichkeit weitgehend unbeachtet – die dafür notwendigen Schritte einzuleiten. Konkret wird Russland per Notifikation mitteilen, nicht mehr Vertragspartei des Energiechartavertrages werden zu wollen. Damit ist auch das Ende der vorläufigen Anwendung des Vertrages durch Russland absehbar. Im Folgenden soll nach einem Überblick über den Energiechartaprozess eine Einschätzung der Entscheidung der russischen Regierung und ihrer Konsequenzen gegeben werden

Screening of Anti-Prion Compounds Using the Protein Misfolding Cyclic Amplification Technology

Prion diseases are 100% fatal infectious neurodegenerative diseases affecting the brains of humans and other mammals. The disease is caused by the formation and replication of prions, composed exclusively of the misfolded prion protein (PrPSc). We invented and developed the protein misfolding cyclic amplification (PMCA) technology for in vitro prion replication, which allow us to replicate the infectious agent and it is commonly used for ultra-sensitive prion detection in biological fluids, tissues and environmental samples. In this article, we studied whether PMCA can be used to screen for chemical compounds that block prion replication. A small set of compounds previously shown to have anti-prion activity in various systems, mostly using cells infected with murine prions, was evaluated for their ability to prevent the replication of prions. Studies were conducted simultaneously with prions derived from 4 species, including human, cattle, cervid and mouse. Our results show that only one of these compounds (methylene blue) was able to completely inhibit prion replication in all species. Estimation of the IC50 for methylene blue inhibition of human prions causing variant Creutzfeldt-Jakob disease (vCJD) was 7.7 μM. Finally, we showed that PMCA can be used for structure-activity relationship studies of anti-prion compounds. Interestingly, some of the less efficient prion inhibitors altered the replication of prions in some species and not others, suggesting that PMCA is useful for studying the differential selectivity of potential drugs

Seed Amplification Assay for the Detection of Pathologic Alpha-Synuclein Aggregates in Cerebrospinal Fluid

Misfolded alpha-synuclein (αSyn) aggregates are a hallmark event in Parkinson’s disease (PD) and other synucleinopathies. Recently, αSyn seed amplification assays (αSyn-SAAs) have shown promise as a test for biochemical diagnosis of synucleinopathies. αSyn-SAAs use the intrinsic self-replicative nature of misfolded αSyn aggregates (seeds) to multiply them in vitro. In these assays, αSyn seeds circulating in biological fluids are amplified by a cyclical process that includes aggregate fragmentation into smaller self-propagating seeds, followed by elongation at the expense of recombinant αSyn (rec-αSyn). Amplification of the seeds allows detection by fluorescent dyes specific for amyloids, such as thioflavin T. Several αSyn-SAA reports have been published in the past under the names ‘protein misfolding cyclic amplification’ (αSyn-PMCA) and ‘real-time quaking-induced conversion’. Here, we describe a protocol for αSyn-SAA, originally reported as αSyn-PMCA, which allows detection of αSyn aggregates in cerebrospinal fluid samples from patients affected by PD, dementia with Lewy bodies or multiple-system atrophy (MSA). Moreover, this αSyn-SAA can differentiate αSyn aggregates from patients with PD versus those from patients with MSA, even in retrospective samples from patients with pure autonomic failure who later developed PD or MSA. We also describe modifications to the original protocol introduced to develop an optimized version of the assay. The optimized version shortens the assay length, decreases the amount of rec-αSyn required and reduces the number of inconclusive results. The protocol has a hands-on time of ~2 h per 96-well plate and can be performed by personnel trained to perform basic experiments with specimens of human origin

The mechanisms of humic substances self-assembly with biological molecules: The case study of the prion protein

Humic substances (HS) are the largest constituent of soil organic matter and are considered as a key component of the terrestrial ecosystem. HS may facilitate the transport of organic and inorganic molecules, as well as the sorption interactions with environmentally relevant proteins such as prions. Prions enter the environment through shedding from live hosts, facilitating a sustained incidence of animal prion diseases such as Chronic Wasting Disease and scrapie in cervid and ovine populations, respectively. Changes in prion structure upon environmental exposure may be significant as they can affect prion infectivity and disease pathology. Despite its relevance, the mechanisms of prion interaction with HS are still not completely understood. The goal of this work is to advance a structural-level picture of the encapsulation of recombinant, non-infectious, prion protein (PrP) into different natural HS. We observed that PrP precipitation upon addition of HS is mainly driven by a mechanism of “salting-out” whereby PrP molecules are rapidly removed from the solution and aggregate in insoluble adducts with humic molecules. Importantly, this process does not alter the protein folding since insoluble PrP retains its α-helical content when in complex with HS. The observed ability of HS to promote PrP insolubilization without altering its secondary structure may have potential relevance in the context of “prion ecology”. These results suggest that soil organic matter interacts with prions possibly without altering the protein structures. This may facilitate prions preservation from biotic and abiotic degradation leading to their accumulation in the environment

Preventive and Therapeutic Reduction of Amyloid Deposition and Behavioral Impairments in a Model of Alzheimer’s Disease by Whole Blood Exchange

Alzheimer\u27s disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (Aβ) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40-80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice. The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of Aβ in plasma soon after blood exchange suggest that mobilization of Aβ from the brain to blood may be implicated. Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

Prions can be detected in blood from patients with variant Creutzfeldt-Jakob disease with high sensitivity and specificity.</jats:p