Lichte Cognitieve Stoornissen (MCI): Prodromen van dementie?

Mild cognitive impairment: a prodromal phase of dementia? Cognitive decline without dementia is common among older persons. A variety of clinical concepts have been introduced in the past 30 years, in order to describe these cognitive deficits arising in older persons. The most frequently used concept is Mild Cognitive Impairment (MCI). MCI is generally seen as a prodromal phase of Alzheimer disease (AD). Several concepts are described, with the neuropsychiatric features and predictors of conversion to dementia c.q. AD. Finally, consequences of preclinically diagnoses for health care are clarified. Tijdschr Gerontol Geriatr 2007; 38:115-121     

L11 domain rearrangement upon binding to RNA and thiostrepton studied by NMR spectroscopy

Ribosomal proteins are assumed to stabilize specific RNA structures and promote compact folding of the large rRNA. The conformational dynamics of the protein between the bound and unbound state play an important role in the binding process. We have studied those dynamical changes in detail for the highly conserved complex between the ribosomal protein L11 and the GTPase region of 23S rRNA. The RNA domain is compactly folded into a well defined tertiary structure, which is further stabilized by the association with the C-terminal domain of the L11 protein (L11_ctd). In addition, the N-terminal domain of L11 (L11_ntd) is implicated in the binding of the natural thiazole antibiotic thiostrepton, which disrupts the elongation factor function. We have studied the conformation of the ribosomal protein and its dynamics by NMR in the unbound state, the RNA bound state and in the ternary complex with the RNA and thiostrepton. Our data reveal a rearrangement of the L11_ntd, placing it closer to the RNA after binding of thiostrepton, which may prevent binding of elongation factors. We propose a model for the ternary L11–RNA–thiostrepton complex that is additionally based on interaction data and conformational information of the L11 protein. The model is consistent with earlier findings and provides an explanation for the role of L11_ntd in elongation factor binding.     

Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX

Proper regulation of intracellular levels of protoporphyrin IX (PPIX), the direct precursor of heme, is important for cell survival. A deficiency in ferrochelatase, which mediates the final step in heme biosynthesis, leads to erythropoietic protoporphyria (EPP), a photosensitivity syndrome caused by the accumulation of PPIX in the skin. We have previously shown that mice with a deficiency in the ABC transporter Bcrp1/Abcg2 display a novel type of protoporphyria. This protoporphyria is mild compared with ferrochelatase-dependent EPP, and in itself not sufficient to cause phototoxicity, but it might exacerbate the consequences of other porphyrias. In this study, we identified the mouse harderian gland as a novel expression site of Bcrp1. Because of its pronounced role in porphyrin secretion, the harderian gland presents a useful tool to study the mechanism of Bcrp1-related protoporphyria and transport of porphyrins. Bcrp1^–/– harderian gland displayed a highly increased accumulation of PPIX glycoconjugates, and a similar shift was seen in Bcrp1^–/– liver. Tear- and hepatobiliary excretion data suggest that Bcrp1 controls intracellular levels of PPIX by mediating high affinity transport of its glycoconjugates and possibly low-affinity transport of unconjugated PPIX. This mechanism may allow cells to prevent or reduce cytotoxicity of PPIX under excess conditions, without spillage under physiological conditions where PPIX is needed. ATP binding cassette transporter; knockout mice; protoporphyria     

ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart

At birth, the heart undergoes a critical metabolic switch from a predominant dependence on carbohydrates during fetal life to a greater dependence on postnatal oxidative metabolism. This remains the principle metabolic state throughout life, although pathologic conditions such as heart failure and cardiac hypertrophy reactivate components of the fetal genetic program to increase carbohydrate utilization. Disruption of the ERRgamma gene (Esrrg), which is expressed at high levels in the fetal and postnatal mouse heart, blocks this switch, resulting in lactatemia, electrocardiographic abnormalities, and death during the first week of life. Genomic ChIP-on-chip and expression analysis identifies ERRgamma as both a direct and an indirect regulator of a nuclear-encoded mitochondrial genetic network that coordinates the postnatal metabolic transition. These findings reveal an unexpected and essential molecular genetic component of the oxidative metabolic gene program in the heart and highlight ERRgamma in the study of cardiac hypertrophy and failure.     

Identification of Phytoplankton from Flow Cytometry Data by Using Radial Basis Function Neural Networks

We describe here the application of a type of artificial neural network, the Gaussian radial basis function (RBF) network, in the identification of a large number of phytoplankton strains from their 11-dimensional flow cytometric characteristics measured by the European Optical Plankton Analyser instrument. The effect of network parameters on optimization is examined. Optimized RBF networks recognized 34 species of marine and freshwater phytoplankton with 91.5% success overall. The relative importance of each measured parameter in discriminating these data and the behavior of RBF networks in response to data from “novel” species (species not present in the training data) were analyzed.     

Design and first results of CytoBuoy: a wireless flow cytometer for in situ analysis of marine and fresh waters.

BACKGROUND:The high costs of microscopical determination and counting of phytoplankton often limit sampling frequencies below an acceptable level for the monitoring of dynamic ecosystems. Although having a limited discrimination power, flow cytometry allows the analysis of large numbers of samples to a level that is sufficient for many basic monitoring jobs. For this purpose, flow cytometers should not be restricted to research laboratories. We report here on the development of an in situ flow cytometer for autonomous operation inside a small moored buoy or on other platforms. METHODS AND RESULTS: Operational specifications served a wide range of applications in the aquatic field. Specific conditions had to be met with respect to the operation platform and autonomy. A small, battery-operated flow cytometer resulted, requiring no external sheath fluid supply. Because it was designed to operate in a buoy, we call it CytoBuoy. Sampling, analysis, and radio transmission of the data proceed automatically at user-defined intervals. A powerful feature is the acquisition and radio transmission of full detector pulse shapes of each particle. This provides valuable morphological information for particles larger than the 5-microm laser focus. CONCLUSIONS:CytoBuoy allows on-line in situ particle analysis, estimation of phytoplankton biomass, and discrimination between different phytoplankton groups. This will increase the applicability of flow cytometry in the field of environmental monitoring.     

Climate change and habitat heterogeneity drive a population increase in Common Buzzards Buteo buteo through effects on survival

The effect of changing climatic conditions on wild populations has been the subject of much recent research. Most attention has been on the direct effects of climate changes on species of lower trophic levels and on the negative consequences of climate change. However, a deeper understanding of how climate change affects apex predators is vital, as they are keystone species that have a disproportionate effect on ecosystems. Studying survival in an apex predator requires individual‐based data from long‐term studies and is complicated by the integration of climatic effects on lower trophic levels. Here we assess how climate affects the survival of the Common Buzzard Buteo buteo. We analysed the survival of 670 males and 669 females over the period 1989–2011, during which time our study population quadrupled. We used mark–recapture survival analysis of individual resightings of breeding adults to identify the environmental factors best explaining survival. A decrease in the North Atlantic Oscillation (NAO) index increased survival to an extent that largely explains the population increase. This might be caused by higher Common Vole Microtus arvalis survival in drier conditions and under snow cover. Buzzard survival appeared to increase more for males than for females, possibly due to the males' higher sensitivity to winter food availability resulting from their smaller body mass. However, we also found that the effect of NAO strongly depended on the area in which individuals lived, especially for females. This may have been caused by the recolonization of Eagle Owls Bubo bubo in some parts of our study area. This study suggests that climatic changes can have complex effects on species of higher trophic levels via an interaction with their prey.     

Monoclonal antibodies for immunohistochemical labeling of immunocompetent cells in frozen sections of rhesus monkey tissues.

Twenty-eight anti-human and two rhesus specific monoclonal antibodies (MAbs) were evaluated for immunohistochemical peroxidase staining reactivity in rhesus monkeys lymph nodes, thymus, liver, and skin allografts. Reactivity with the following antigens was assessed: MHC class I, II-DR, -DQ, and -DP antigens; leukocyte markers CD1, CD2, CD3, CD4, CD8, CD14, CD16, CD25, CD57; a proliferation associated nuclear antigen; interferon-gamma and tumor necrosis factor-alpha. Twenty-three MAbs proved to be suitable for immunohistochemical staining on frozen sections.