Compensation for Retinal Vessel Density Reduces the Variation of Circumpapillary RNFL in Healthy Subjects

This work intends to assess circumpapillary retinal vessel density (RVD) at a 3.46 mm diameter circle and correlate it with circumpapillary retinal nerve fiber layer (RNFL) thickness measured with Fourier-Domain Optical Coherence Tomography. Furthermore, it aims to evaluate the reduction of intersubject variability of RNFL when considering RVD as a source of information for RNFL distribution. For that, 106 healthy subjects underwent circumpapillary RNFL measurement. Using the scanning laser ophthalmoscope fundus image, thickness and position of retinal vessels were assessed and integrated in a 256-sector RVD profile. The relationship between local RVD value and local RNFL thickness was modeled by linear regression. RNFL was then compensated for RVD variation by regression formulas. A strong statistically significant intrasubject correlation was found for all subjects between RVD and RNFL profiles (mean R = 0.769). In the intersubject regression analysis, 247 of 256 RNFL sectors showed a statistically significant positive correlation with RVD (mean R = 0.423). RVD compensation of RNFL resulted in a relative reduction of up to 20% of the intersubject variance. In conclusion, RVD in a 3.46mm circle has a clinically relevant influence on the RNFL distribution. RVD may be used to develop more individualized normative values for RNFL measurement, which might improve early diagnosis of glaucoma.     

Fat facets does a Highwire act at the synapse.

Neuromuscular synapses are highly dynamic structures that respond to both intercellular and intracellular cues to manipulate synaptic form. A variety of post-translational modifications of synaptic proteins are used to regulate synaptic plasticity. A recent report by DiAntonio et al. shows that two ubiquitin pathway proteins, Highwire and Fat facets, may be mutually antagonistic regulators of presynaptic growth at the Drosophila neuromuscular junction. This work adds support to the emerging idea that ubiquitin, a polypeptide that targets proteins for proteasomal degradation, regulates synaptic development.     

Mutation of Threonine 34 in Mouse Podoplanin-Fc Reduces CLEC-2 Binding and Toxicity in Vivo While Retaining Anti-lymphangiogenic Activity

The lymphatic system plays an important role in cancer metastasis and inhibition of lymphangiogenesis could be valuable in fighting cancer dissemination. Podoplanin (Pdpn) is a small, transmembrane glycoprotein expressed on the surface of lymphatic endothelial cells (LEC). During mouse development, binding of Pdpn to the C-type lectin-like receptor 2 (CLEC-2) on platelets is critical for the separation of the lymphatic and blood vascular systems. Competitive inhibition of Pdpn functions with a soluble form of the protein, Pdpn-Fc, leads to reduced lymphangiogenesis in vitro and in vivo. However, the transgenic overexpression of human Pdpn-Fc in mouse skin causes disseminated intravascular coagulation due to platelet activation via CLEC-2. In the present study, we produced and characterized a mutant form of mouse Pdpn-Fc, in which threonine 34, which is considered essential for CLEC-2 binding, was mutated to alanine (PdpnT34A-Fc). Indeed, PdpnT34A-Fc displayed a 30-fold reduced binding affinity for CLEC-2 compared with Pdpn-Fc. This also translated into fewer side effects due to platelet activation in vivo. Mice showed less prolonged bleeding time and fewer embolized vessels in the liver, when PdpnT34A-Fc was injected intravenously. However, PdpnT34A-Fc was still as active as wild-type Pdpn-Fc in inhibiting lymphangiogenesis in vitro and also inhibited lymphangiogenesis in vivo. These data suggest that the function of Pdpn in lymphangiogenesis does not depend on threonine 34 in the CLEC-2 binding domain and that PdpnT34A-Fc might be an improved inhibitor of lymphangiogenesis with fewer toxic side effects.     

Affect and Cognition in Attitude Formation toward Familiar and Unfamiliar Attitude Objects

At large attitudes are built on earlier experience with the attitude object. If earlier experiences are not available, as is the case for unfamiliar attitude objects such as new technologies, no stored evaluations exist. Yet, people are still somehow able to construct attitudes on the spot. Depending on the familiarity of the attitude object, attitudes may find their basis more in affect or cognition. The current paper investigates differences in reliance on affect or cognition in attitude formation toward familiar and unfamiliar realistic attitude objects. In addition, individual differences in reliance on affect (high faith in intuition) or cognition (high need for cognition) are taken into account. In an experimental survey among Dutch consumers (N = 1870), we show that, for unfamiliar realistic attitude objects, people rely more on affect than cognition. For familiar attitude objects where both affective and cognitive evaluations are available, high need for cognition leads to more reliance on cognition, and high faith in intuition leads to more reliance on affect, reflecting the influence of individually preferred thinking style. For people with high need for cognition, cognition has a higher influence on overall attitude for both familiar and unfamiliar realistic attitude objects. On the other hand, affect is important for people with high faith in intuition for both familiar and unfamiliar attitude objects and for people with low faith in intuition for unfamiliar attitude objects; this shows that preferred thinking style is less influential for unfamiliar objects. By comparing attitude formation for familiar and unfamiliar realistic attitude objects, this research contributes to understanding situations in which affect or cognition is the better predictor of overall attitudes.     

Bending stiffness of lipid bilayers: IV. Interpretation of red cell shape change.

Two mechanisms are operative when the resting shape of human red cells is changed into an echinocyte or a stomatocyte. The first (bilayer couple) is a differential change in the surface area of the two monolayers. It rests on the two-dimensional isotropic elasticity of the two monolayers and their fixed distance. The second (single layer) is a change in the average cone angle of the molecules comprising a monolayer. It rests on the intrinsic bending elasticity of each single layer. With a few exceptions the first mechanism has been quoted to interpret experimentally observed shape changes. To reconsider this preference two types of spontaneous curvatures (in bilayer couple bending and in single-layer bending) are defined. It is shown that (a) disregarding the single-layer mechanism is not justified and (b) there is too little basic information for quantitative interpretations of shape change.     

Toll-like receptor 4 deficiency: Smaller infarcts,but nogain in function

Backgound  

It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion (MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed compared to wild type (WT).     

Diploid Amazon mollies (Poecilia formosa) show a higher fitness than triploids in clonal competition experiments

The gynogenetic livebearing Amazon molly (Poecilia formosa) is a sexual parasite that exploits males of closely related species for sperm. This is needed as physiological stimulus for embryo development; however, none of the male’s genes are normally incorporated into the genome of the gynogenetic offspring. Mostly diploid individuals were reported from the natural habitats in North-Eastern Mexico and South-Eastern Texas but stable populations of triploids have been reported from the Río Soto la Marina drainage and in the Río Guayalejo in North-Eastern Mexico. Triploidy is the result of defects in the mechanisms that normally clear the host sperm from the ameiotic diploid egg. Triploids also reproduce gynogenetically and their frequencies fluctuate markedly between years, seasons, and localities. To understand the dynamics of this mating system, it is important to understand the relative reproductive success of triploids and diploids. We hypothesize that triploids should have a selective advantage over diploids due to heterosis and/or gene redundancy based on the additional genetic material from the sexual host. However, clonal competition experiments revealed a clear reproductive advantage of diploids competing with triploids. This result contradicts not only our hypothesis but also the stable co-existence of diploids and triploids in natural habitats. Frequency dependent selection, niche partitioning and environmental heterogeneity are discussed as possible explanations.