Mycobacteria exploit nitric oxide‐induced transformation of macrophages into permissive giant cells

Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so‐called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double‐edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO‐induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria‐infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state.     

Epizoochory by large herbivores: merging data with models

The dispersal of plant seeds in the fur of large herbivores (epizoochory) is an important but complex long-distance dispersal mechanism. We developed a spatially explicit simulation model of epizoochorous seed dispersal, which was parameterized based on empirical studies of the movement and behaviour of donkeys, and the distribution, seed production, seed accessibility, seed adhesion, and seed retention on donkey fur of selected plant species in a coastal dune nature reserve in Flanders, Belgium. We compared predicted and observed seed numbers of the 14 plant species on donkey fur.

Modelled seed shadows indicate that for most species about half of all seeds dispersed by donkeys should travel a net distance of >100 m, and about 1% should travel >500 m within this more or less isodiametric 100 ha nature reserve. Seeds with longer retention times are expected to travel further than those with short retention times. Enlarging the reserve area had little impact on the forecasted dispersal distances.

Variation among plant species in the observed seed numbers found on donkey fur were well predicted by the model (R²=0.56, P=0.002), though the predictions relied on relatively crude estimates of seed production and accessibility to donkeys, indicating that more accurate estimates of these parameters are needed.

Our model confirms the important role of epizoochory in affecting long-distance seed dispersal, and provides a modelling framework for integrating the multiple components of the dispersal process.     

A Single Intravenous AAV9 Injection Mediates Bilateral Gene Transfer to the Adult Mouse Retina

Widespread gene delivery to the retina is an important challenge for the treatment of retinal diseases, such as retinal dystrophies. We and others have recently shown that the intravenous injection of a self-complementary (sc) AAV9 vector can direct efficient cell transduction in the central nervous system, in both neonatal and adult animals. We show here that the intravenous injection of scAAV9 encoding green fluorescent protein (GFP) resulted in gene transfer to all layers of the retina in adult mice, despite the presence of a mature blood-eye barrier. Cell morphology studies and double-labeling with retinal cell-specific markers showed that GFP was expressed in retinal pigment epithelium cells, photoreceptors, bipolar cells, Müller cells and retinal ganglion cells. The cells on the inner side of the retina, including retinal ganglion cells in particular, were transduced with the highest efficiency. Quantification of the cell population co-expressing GFP and Brn-3a showed that 45% of the retinal ganglion cells were efficiently transduced after intravenous scAAV9-GFP injection in adult mice. This study provides the first demonstration that a single intravenous scAAV9 injection can deliver transgenes to the retinas of both eyes in adult mice, suggesting that this vector serotype is able to cross mature blood-eye barriers. This intravascular gene transfer approach, by eliminating the potential invasiveness of ocular surgery, could constitute an alternative when fragility of the retina precludes subretinal or intravitreal injections of viral vectors, opening up new possibilities for gene therapy for retinal diseases.     

Local variation in conspecific plant density influences plant–soil feedback in a natural grassland

Several studies have argued that under field conditions plant–soil feedback may be related to the local density of a plant species, but plant–soil feedback is often studied by comparing conspecific and heterospecific soils or by using mixed soil samples collected from different locations and plant densities. We examined whether the growth of the early successional species Jacobaea vulgaris in soil collected from the field is related to the local variation in plant density of this species. In a grassland restoration site, we selected eight 8 m × 8 m plots, four with high and four with low densities of J. vulgaris plants. In 16 subplots in each plot we recorded the density and size of J. vulgaris, and characteristics of the vegetation and the soil chemistry. Soil collected from each subplot was used in a greenhouse pot-experiment to study the growth of J. vulgaris, both in pure field soil and in sterile soil inoculated with a small part of field soil.In the field, flowering J. vulgaris plants were taller, the percentage of rosette plants was higher and seed density was larger in High- than in Low-density plots. In the pot experiment, J. vulgaris had a negative plant–soil feedback, but biomass was also lower in soil collected from High- than from Low-density plots, although only when growing in inoculated soil. Regression analyses showed that J. vulgaris biomass of plants growing in pure soil was related to soil nutrients, but also to J. vulgaris density in the field.We conclude that in the field there is local variation in the negative plant–soil feedback of J. vulgaris and that this variation can be explained by the local density of J. vulgaris, but also by other factors such as nutrient availability.     

Small,dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipoprotein A‐I

Plasma high‐density lipoproteins (HDLs) protect endothelial cells against apoptosis induced by oxidized low‐density lipoprotein (oxLDL). The specific component(s) of HDLs implicated in such cytoprotection remain(s) to be identified. Human microvascular endothelial cells (HMEC‐1) were incubated with mildly oxLDL in the presence or absence of each of five physicochemically distinct HDL subpopulations fractionated from normolipidemic human plasma (n= 7) by isopycnic density gradient ultracentrifugation. All HDL subfractions protected HMEC‐1 against oxLDL‐induced primary apoptosis as revealed by nucleic acid staining, annexin V binding, quantitative DNA fragmentation, inhibition of caspase‐3 activity and reduction of cytoplasmic release of cytochrome c and apoptosis‐inducing factor. Small, dense HDL 3c displayed twofold superior intrinsic cytoprotective activity (as determined by mitochondrial dehydrogenase activity) relative to large, light HDL 2b on a per particle basis (P < 0.05). Equally, all HDL subfractions attenuated intracellular generation of reactive oxygen species (ROS); such anti‐oxidative activity diminished from HDL 3c to HDL 2b. The HDL protein moiety, in which apolipoprotein A‐I (apoA‐I) predominated, accounted for ～70% of HDL anti‐apoptotic activity. Furthermore, HDL reconstituted with apoA‐I, cholesterol and phospholipid potently protected HMEC‐1 from apoptosis. By contrast, modification of the content of sphingosine‐1‐phosphate in HDL did not significantly alter cytoprotection. We conclude that small, dense, lipid‐poor HDL 3 potently protects endothelial cells from primary apoptosis and intracellular ROS generation induced by mildly oxLDL, and that apoA‐I is pivotal to such protection.     

Do You Hear the Same? Cardiorespiratory Responses between Mothers and Infants during Tonal and Atonal Music

This study examined the effects of tonal and atonal music on respiratory sinus arrhythmia (RSA) in 40 mothers and their 3-month-old infants. The tonal music fragment was composed using the structure of a harmonic series that corresponds with the pitch ratio characteristics of mother–infant vocal dialogues. The atonal fragment did not correspond with a tonal structure. Mother–infant ECG and respiration were registered along with simultaneous video recordings. RR-interval, respiration rate, and RSA were calculated. RSA was corrected for any confounding respiratory and motor activities. The results showed that the infants’ and the mothers’ RSA-responses to the tonal and atonal music differed. The infants showed significantly higher RSA-levels during the tonal fragment than during the atonal fragment and baseline, suggesting increased vagal activity during tonal music. The mothers showed RSA-responses that were equal to their infants only when the infants were lying close to their bodies and when they heard the difference between the two fragments, preferring the tonal above the atonal fragment. The results are discussed with regard to music-related topics, psychophysiological integration and mother-infant vocal interaction processes.