ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke

Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2^wt) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP^wt) and its phosphorylation-deficient mutant RKIP^S153A, known inhibitors of the ERK1/2 signaling cascade. RKIP^wt and RKIP^S153A attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.     

Interaction of Alpha Synuclein and Microtubule Organization Is Linked to Impaired Neuritic Integrity in Parkinson’s Patient-Derived Neuronal Cells

Parkinson’s disease (PD) is neuropathologically characterized by the loss of dopaminergic neurons and the deposition of aggregated alpha synuclein (aSyn). Mounting evidence suggests that neuritic degeneration precedes neuronal loss in PD. A possible underlying mechanism could be the interference of aSyn with microtubule organization in the neuritic development, as implied by several studies using cell-free model systems. In this study, we investigate the impact of aSyn on microtubule organization in aSyn overexpressing H4 neuroglioma cells and midbrain dopaminergic neuronal cells (mDANs) generated from PD patient-derived human induced pluripotent stem cells (hiPSCs) carrying an aSyn gene duplication (SNCA^Dupl). An unbiased mass spectrometric analysis reveals a preferential binding of aggregated aSyn conformers to a number of microtubule elements. We confirm the interaction of aSyn with beta tubulin III in H4 and hiPSC-derived mDAN cell model systems, and demonstrate a remarkable redistribution of tubulin isoforms from the soluble to insoluble fraction, accompanied by a significantly increased insoluble aSyn level. Concordantly, SNCA^Dupl mDANs show impaired neuritic phenotypes characterized by perturbations in neurite initiation and outgrowth. In summary, our findings suggest a mechanistic pathway, through which aSyn aggregation interferes with microtubule organization and induces neurite impairments.     

ERG1, encoding squalene epoxidase,is located on the right arm of chromosome VII of Saccharomyces cerevisiae

The ERG1 gene of Saccharomyces cerevisiae encodes squalene epoxidase, a key enzyme in the ergosterol pathway. ERG1 is an essential gene. Disruption of the gene with URA3 results in a lethal phenotype when cells are grown under aerobic conditions, even in the presence of ergosterol. However, cells are viable in the presence of ergosterol under anaerobic growth conditions during which ergosterol is taken up by cells. Physical and genetic mapping data reveal that ERG1 is located on the right arm of chromosome VII proximal to QCR9 at a distance of 14·6 cM from ADE3.     

Detailed depth profiles of sulfate ingress into concrete measured with laser induced breakdown spectroscopy

Sulfate attack constitutes a major risk of chemical aggression for concrete and other building materials. Mainly structures exposed to sewage waters and sulfate rich soils are affected. The measurement of sulfate ingress is important for damage assessment previous to repair works and for quality assurance of the effectiveness of protecting coatings or during concrete removal.Laser induced breakdown spectroscopy is introduced for the quantitative measurement of sulfur contents in building materials, providing detailed depth profiles and imaging element distributions with 1 mm spatial resolution. Detailed statistical evaluation is possible due to the spatial resolution and the fast measurement of the method. Practical applications of the method for damage assessment are demonstrated for three different sewage plants.     

The reliability of third-party certification in the food chain: From checklists to risk-oriented auditing

In recent years, certification has become increasingly relevant for agribusiness. In Europe, substantial parts of the value chain are already being certified by standards such as the International Food Standard (IFS) or GLOBALGAP (the former EurepGap). It is not known, however, whether these approaches can de facto ensure high quality control. This article is based on a database analysis of the German certification system Quality and Safety (QS) and a workshop with the QS-certification bodies conducting 85% of all agricultural audits. It seeks to deduce the first empirical hypotheses concerned with the connection between the reliability of third-party certification and the institutional framing of standards.     

Comparison of three methods for detecting Campylobacter spp. in chilled or frozen meat

There is a demand from the meat industry as well as from public health authorities for a simple and rapid detection method for thermophilic Campylobacter spp. from food. Hence, we compared different isolation procedures for their usefulness for this purpose. Bolton enrichment medium without blood, incubated statically in stomacher bags in microaerophilic atmosphere, detected more samples positive for thermophilic Campylobacter spp. than did Preston enrichment broth in bottles with small headspace and tight caps, incubated in aerobic atmosphere. Use of an automated antigen detection system to identify enrichment cultures positive for Campylobacter spp. was as sensitive as selective agars, and reduced the detection time by 24 h. Campylobacter spp. were recovered from 18.4% of the 461 samples tested. The prevalence was highest in refrigerated poultry meat (52% of the 80 samples tested) and poultry offal (41% of the 44 samples tested).     

Insect‐Specific Production of New GameXPeptides in Photorhabdus luminescens TTO1, Widespread Natural Products in Entomopathogenic Bacteria

Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect‐specific production of the new GameXPeptides E–H ( 5 – 8 ) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions.     

The Balance Between Reactivity and Stability of Modified Oxide Surfaces Illustrated by the Behavior of Sulfated Zirconia Catalysts

The stability of a series of sulfated zirconia catalysts, promoted with up to 2 wt% iron or manganese, in their calcined state was investigated. Phase composition, nature of surface sulfate species, degree of hydroxylation, and butane isomerization activity changed during aging over months in various atmospheres and during milling. The metastability of small oxide particles is discussed, including literature data on alumina, titania and other oxides. Catalytically active fractions of a material easily transition into more stable, less active forms.     

Relative bioavailability of coumarin from cinnamon and cinnamon-containing foods compared to isolated coumarin: a four-way crossover study in human volunteers

Scope: Cassia cinnamon contains high levels (up to 1 %) of coumarin. Heavy consumption of this spice may result in a dose exceeding the tolerable daily intake (TDI). In this context, the question was raised whether coumarin in the plant matrix of cinnamon has the same bioavailability as isolated coumarin. Methods and results: A four‐way crossover study was performed, in which the same dose of 12 mg coumarin was administered in different formulations to 24 healthy volunteers. The relative extent of absorption measured as urinary excretion of the main metabolite 7‐hydroxycoumarin (7OHC) was found to be 62.8% for isolated coumarin in a capsule (reference), 56.0% for cinnamon in capsules, 66.1% for cinnamon tea, and 54.7% for cinnamon in rice pudding (means, n=23, observation period 8 hours). Additionally, 7OHC plasma levels were measured for 105 minutes after administration and revealed a fast absorption of coumarin from cinnamon tea leading to the highest peak concentrations. Conclusion: The relative extent of absorption of coumarin from powder of cassia cinnamon is only slightly lower than that of isolated coumarin. Therefore, the TDI of coumarin can be used for risk assessment of coumarin exposure from cinnamon‐containing meals.