“Ik kan mijn acceptgiro niet meer invullen”

Visual problems occur frequently in elderly patients and are often caused by ophthalmological problems. In this clinical lesson we show that visual problems can also be caused by posterior cortical atrophy (PCA). PCA is a clinico-radiological syndrome that is often caused by Alzheimer’s disease and other neurodegenerative diseases as Lewy body dementia and corticobasal degeneration. It is characterized by progressive decline in visual information processing. In addition, there is relative retention of memory and language in early stages. Brain imaging shows atrophy of the posterior brain areas.     

Introducing fluorescence resonance energy transfer‐based biosensors for the analysis of cAMP‐PKA signalling in the fungal pathogen Candida glabrata

The cyclic adenosine monophosphate‐protein kinase A (cAMP‐PKA) pathway is central to signal transduction in many organisms. In pathogenic fungi such as Candida albicans, this signalling cascade has proven to be involved in several processes, such as virulence, indicating its potential importance in antifungal drug discovery. Candida glabrata is an upcoming pathogen of the same species, yet information regarding the role of cAMP‐PKA signalling in virulence is largely lacking. To enable efficient monitoring of cAMP‐PKA activity in this pathogen, we here present the usage of two FRET‐based biosensors. Both variations in the activity of PKA and the quantity of cAMP can be detected in a time‐resolved manner, as we exemplify by glucose‐induced activation of the pathway. We also present information on how to adequately process and analyse the data in a mathematically correct and physiologically relevant manner. These sensors will be of great benefit for scientists interested in linking the cAMP‐PKA signalling cascade to downstream processes, such as virulence, possibly in a host environment.     

Human lactoferrin receptor activity in non-encapsulated Haemophilus influenzae

Since the ability of bacteria to compete with lactoferrin for iron contributes to the pathogenesis of mucosal infections, the presence of lactoferrin receptor activity in non-encapsulated Haemophilus influenzae was investigated. The growth of 18 H. influenzae isolates from the sputum samples of chronic bronchitis patients and of six of seven H. influenzae throat isolates from healthy adults was stimulated by iron saturated human lactoferrin. Apo-lactoferrin did not stimulate the growth of H. influenzae. Human lactoferrin binding to iron limited bacteria was detected for 16 H. influenzae strains from chronic bronchitis patients and for five of seven isolates from healthy adults. We conclude that the majority of H. influenzae isolates tested bind human lactoferrin and that the iron from lactoferrin is used for growth.     

Gap pattern and colonization opportunities in plant communities: effects of species richness, mortality, and spatial aggregation

We investigate how perturbations that induce mortality transform original spatial patterns in plant communities into binary spatial patterns of survivors and perished individuals. By means of computer simulation, we analyse effects of average mortality, interspecific variation of mortality around the mean, spatial distribution of the species (clumping degree), and species richness. Gap spatial pattern is quantified by four spatial indices or landscape metrics (gap area, density, shape and coherence). In single‐species communities, the emerging gap patterns are subject to critical phenomena: opportunities for colonizers to establish increase with mortality, but more rapidly at specific mortality thresholds. In multi‐species communities, neither species richness nor interspecific variation of mortality influences gap spatial pattern when community assembly is random. Colonization opportunities would therefore not be affected by local species extinction in such a system, nor by the presence of species with divergent sensitivities to perturbation. In a community that is highly spatially aggregated, increases in interspecific mortality variation shift the pattern towards fewer gaps that are larger and more isodiametric, which suggests increased establishment chances for colonizers. Similar changes are induced in communities characterized by large interspecific mortality differences if clumping degree is increased. Loss of species richness only modifies gap spatial pattern to a substantial extent if mortality variation is high: in this case, depauperate communities exhibit a wider variety of colonization opportunities (more gaps which are on average smaller, but the largest gap is larger) than species‐richer ones. These findings may explain the contrast between the negative diversity‐invasibility relationship often found in small‐scale experimental studies and the positive diversity‐invasibility relationship found in observational studies at larger scale. They also demonstrate that the pre‐disturbance spatial structure of a community significantly affects colonization opportunities for alien species, and is therefore a likely determinant of the trajectory of secondary succession following perturbation.     

Interleukin-17A mediates acquired immunity to pneumococcal colonization

Although anticapsular antibodies confer serotype-specific immunity to pneumococci, children increase their ability to clear colonization before these antibodies appear, suggesting involvement of other mechanisms. We previously reported that intranasal immunization of mice with pneumococci confers CD4+ T cell-dependent, antibody- and serotype-independent protection against colonization. Here we show that this immunity, rather than preventing initiation of carriage, accelerates clearance over several days, accompanied by neutrophilic infiltration of the nasopharyngeal mucosa. Adoptive transfer of immune CD4+ T cells was sufficient to confer immunity to na?ve RAG1(-/-) mice. A critical role of interleukin (IL)-17A was demonstrated: mice lacking interferon-gamma or IL-4 were protected, but not mice lacking IL-17A receptor or mice with neutrophil depletion. In vitro expression of IL-17A in response to pneumococci was assayed: lymphoid tissue from vaccinated mice expressed significantly more IL-17A than controls, and IL-17A expression from peripheral blood samples from immunized mice predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of tonsillar cells of children or adult blood but not cord blood. IL-17A increased pneumococcal killing by human neutrophils both in the absence and in the presence of antibodies and complement. We conclude that IL-17A mediates pneumococcal immunity in mice and probably in humans; its elicitation in vitro could help in the development of candidate pneumococcal vaccines.     

Preventive action of organosilicon treatments against disfigurement of wood under laboratory and outdoor conditions

Organosilicons and biocides with known effectiveness against fungal disfigurement were used for dipping or impregnating Scots pine sapwood specimens. All specimens were artificially or naturally weathered and the colour of all specimens was determined with a spectrophotometer at fixed times. After artificial weathering the specimens were used in blue stain tests according to EN 152 or according to the EN 152 reverse method. The naturally exposed specimens were inspected for fungal disfigurement on their back side. Although the results learn that the coating approach is far better than the wood preservatives approach for evaluating blue stain attack of organosilicon-treated wood, organosilicons fail to protect wood under laboratory conditions. Outdoor exposure, however, revealed that organosilicon impregnated specimens were better protected against fungal disfigurement. The addition of a biocide improves the performance. Artificially aged specimens did not show significant colour differences compared to untreated Scots pine sapwood, while naturally aged specimens did, depending on the treatment conditions and presence of biocides. Organosilicons are able to reduce leaching of (degraded) wood constituents, leading to fewer colour changes compared to untreated scots pine and to decreased availability of nutrients for superficial fungal growth.