The Effects of Exosomes on the Regeneration of Rat Calvaria

Periodontal disease is a bacterial induced chronic inflammatory condition that occurs in a susceptible host, affecting the teeth, gingiva, periodontal ligament, and alveolar bone. The resultant pathological bone defects often require surgical intervention, with the ultimate goal being regeneration of the periodontium through the application of grafting materials and biologics. Mesenchymal stem cells (MSCs) show great potential in regenerative medicine for their ability to enhance cell proliferation and differentiation, increase angiogenesis, and modulate the immune response. Stem cell-derived by-products, known as exosomes are a specific class of lipid-membrane-bound extracellular vesicles that are proliferative and chemotactic, are able to inhibit cytokine production, and may suppress differentiation of osteoclasts. The aim of this study is to determine if the delivery of exosomes into rat calvarial defects will increase regeneration by reducing the residual defect area and enhancing bone volume. Male Sprague-Dawley rats with bilateral 5mm surgically-created calvarial defects were randomized into groups and treated with low- and high-dose exosome suspensions via a collagen gel matrix or a PBS-soaked collagen control. After 4 weeks, the calvaria were harvested and analyzed via micro computed tomography (micro-CT). Volumetric micro-CT analysis showed that defects treated with high-dose exosomes displayed a trend towards enhanced bone healing. Based on the results of this pilot study, treatment with exosomes could be a promising therapeutic approach for treatment of bone defects

Low-velocity collisions of centimeter-sized dust aggregates

Collisions between centimeter- to decimeter-sized dusty bodies are important to understand the mechanisms leading to the formation of planetesimals. We thus performed laboratory experiments to study the collisional behavior of dust aggregates in this size range at velocities below and around the fragmentation threshold. We developed two independent experimental setups with the same goal to study the effects of bouncing, fragmentation, and mass transfer in free particle-particle collisions. The first setup is an evacuated drop tower with a free-fall height of 1.5 m, providing us with 0.56 s of microgravity time so that we observed collisions with velocities between 8 mm/s and 2 m/s. The second setup is designed to study the effect of partial fragmentation (when only one of the two aggregates is destroyed) and mass transfer in more detail. It allows for the measurement of the accretion efficiency as the samples are safely recovered after the encounter. Our results are that for very low velocities we found bouncing as could be expected while the fragmentation velocity of 20 cm/s was significantly lower than expected. We present the critical energy for disruptive collisions Q*, which showed up to be at least two orders of magnitude lower than previous experiments in the literature. In the wide range between bouncing and disruptive collisions, only one of the samples fragmented in the encounter while the other gained mass. The accretion efficiency in the order of a few percent of the particle's mass is depending on the impact velocity and the sample porosity. Our results will have consequences for dust evolution models in protoplanetary disks as well as for the strength of large, porous planetesimal bodies

Progress Report on Iowa State University Burroughs Endowment Activities

Faculty in the Department of Animal Science initiated soliciting of funds in 1987 to establish a permanent endowment to recognize the distinguished career and major contributions of Dr. Wise Burroughs, a distinguished professor in animal science at Iowa State University. The endowment was established in the Iowa State University Foundation in 1991. The purpose of the fund is to support research and graduate education in the areas of fundamental factors regulating growth in food-producing animals, with emphasis on ruminants; to enhance growth of animals with the goal of improving the competitive position of ruminants as food-producing animals; and to develop innovative approaches to ruminant nutrition and/or growth enhancement as a means to improve desirability of meat produced by food animals. Dr. Burroughs’ research resulted in important and significant developments in technology for modern production systems for beef cattle. He was widely known for his ability to communicate complex ideas and research results for use by those involved in the animal industry. The current Burroughs Team has established three research projects: 1) Ghrelin--How does ghrelin affect blood and body composition in rats?; 2) Use of 25- hydroxyvitamin D3 to improve tenderness of beef; 3) Redesigning beef cattle to have a more healthful fatty acid composition

Crossing barriers in planetesimal formation: The growth of mm-dust aggregates with large constituent grains

Collisions of mm-size dust aggregates play a crucial role in the early phases of planet formation. We developed a laboratory setup to observe collisions of dust aggregates levitating at mbar pressures and elevated temperatures of 800 K. We report on collisions between basalt dust aggregates of from 0.3 to 5 mm in size at velocities between 0.1 and 15 cm/s. Individual grains are smaller than 25 \mum in size. We find that for all impact energies in the studied range sticking occurs at a probability of 32.1 \pm 2.5% on average. In general, the sticking probability decreases with increasing impact parameter. The sticking probability increases with energy density (impact energy per contact area). We also observe collisions of aggregates that were formed by a previous sticking of two larger aggregates. Partners of these aggregates can be detached by a second collision with a probability of on average 19.8 \pm 4.0%. The measured accretion efficiencies are remarkably high compared to other experimental results. We attribute this to the rel. large dust grains used in our experiments, which make aggregates more susceptible to restructuring and energy dissipation. Collisional hardening by compaction might not occur as the aggregates are already very compact with only 54 \pm 1% porosity. The disassembly of previously grown aggregates in collisions might stall further aggregate growth. However, owing to the levitation technique and the limited data statistics, no conclusive statement about this aspect can yet be given. We find that the detachment efficiency decreases with increasing velocities and accretion dominates in the higher velocity range. For high accretion efficiencies, our experiments suggest that continued growth in the mm-range with larger constituent grains would be a viable way to produce larger aggregates, which might in turn form the seeds to proceed to growing planetesimals.Comment: 9 pages, 20 figure

The plasmodium lactate/H+ transporter PfFNT is essential and druggable in vivo

Malaria parasites in the blood stage express a single transmembrane transport protein for the release of the glycolytic end product l-lactate/H(+) from the cell. This transporter is a member of the strictly microbial formate-nitrite transporter (FNT) family and a novel putative drug target. Small, drug-like FNT inhibitors potently block lactate transport and kill Plasmodium falciparum parasites in culture. The protein structure of Plasmodium falciparum FNT (PfFNT) in complex with the inhibitor has been resolved and confirms its previously predicted binding site and its mode of action as a substrate analog. Here, we investigated the mutational plasticity and essentiality of the PfFNT target on a genetic level, and established its in vivo druggability using mouse malaria models. We found that, besides a previously identified PfFNT G107S resistance mutation, selection of parasites at 3 x IC(50) (50% inhibitory concentration) gave rise to two new point mutations affecting inhibitor binding: G21E and V196L. Conditional knockout and mutation of the PfFNT gene showed essentiality in the blood stage, whereas no phenotypic defects in sexual development were observed. PfFNT inhibitors mainly targeted the trophozoite stage and exhibited high potency in P. berghei- and P. falciparum-infected mice. Their in vivo activity profiles were comparable to that of artesunate, demonstrating strong potential for the further development of PfFNT inhibitors as novel antimalarials

An archaeology of borders: qualitative political theory as a tool in addressing moral distance

Interviews, field observations and other qualitative methods increasingly are being used to inform the construction of arguments in normative political theory. This article works to demonstrate the strong salience of some kinds of qualitative material for cosmopolitan arguments to extend distributive boundaries. The incorporation of interviews and related qualitative material can make the moral claims of excluded others more vivid and possibly more difficult to dismiss by advocates of strong priority to compatriots in distributions. Further, it may help to promote the kind of perspective taking that has been associated with actually motivating a willingness to aid by individuals. Illustrative findings are presented from field work conducted for a normative project on global citizenship, including interviews with unauthorized immigrants and the analysis of artifacts left behind on heavily used migrant trails

A simple model for the evolution of the dust population in protoplanetary disks

Context: The global size and spatial distribution of dust is an important ingredient in the structure and evolution of protoplanetary disks and in the formation of larger bodies, such as planetesimals. Aims: We aim to derive simple equations that explain the global evolution of the dust surface density profile and the upper limit of the grain size distribution and which can readily be used for further modeling or for interpreting of observational data. Methods: We have developed a simple model that follows the upper end of the dust size distribution and the evolution of the dust surface density profile. This model is calibrated with state-of-the-art simulations of dust evolution, which treat dust growth, fragmentation, and transport in viscously evolving gas disks. Results: We find very good agreement between the full dust-evolution code and the toy model presented in this paper. We derive analytical profiles that describe the dust-to-gas ratios and the dust surface density profiles well in protoplanetary disks, as well as the radial flux by solid material "rain out", which is crucial for triggering any gravity assisted formation of planetesimals. We show that fragmentation is the dominating effect in the inner regions of the disk leading to a dust surface density exponent of -1.5, while the outer regions at later times can become drift-dominated, yielding a dust surface density exponent of -0.75. Our results show that radial drift is not efficient in fragmenting dust grains. This supports the theory that small dust grains are resupplied by fragmentation due to the turbulent state of the disk.Comment: 12 pages, 10 figures, accepted to A&

High (but Not Low) Urinary Iodine Excretion Is Predicted by Iodine Excretion Levels from Five Years Ago

Background: It has not been investigated whether there are associations between urinary iodine (UI) excretion measurements some years apart, nor whether such an association remains after adjustment for nutritional habits. The aim of the present study was to investigate the relation between iodine-creatinine ratio (ICR) at two measuring points 5 years apart. Methods: Data from 2,659 individuals from the Study of Health in Pomerania were analyzed. Analysis of covariance and Poisson regressions were used to associate baseline with follow-up ICR. Results: Baseline ICR was associated with follow-up ICR. Particularly, baseline ICR >300 mu g/g was related to an ICR >300 mu g/g at follow-up (relative risk, RR: 2.20; p < 0.001). The association was stronger in males (RR: 2.64; p < 0.001) than in females (RR: 1.64; p = 0.007). In contrast, baseline ICR <100 mu g/g was only associated with an ICR <100 mu g/g at follow-up in males when considering unadjusted ICR. Conclusions: We detected only a weak correlation with respect to low ICR. Studies assessing iodine status in a population should take into account that an individual with a low UI excretion in one measurement is not necessarily permanently iodine deficient. On the other hand, current high ICR could have been predicted by high ICR 5 years ago. Copyright (C) 2011 S. Karger AG, Base

Inferring PDZ Domain Multi-Mutant Binding Preferences from Single-Mutant Data

Many important cellular protein interactions are mediated by peptide recognition domains. The ability to predict a domain's binding specificity directly from its primary sequence is essential to understanding the complexity of protein-protein interaction networks. One such recognition domain is the PDZ domain, functioning in scaffold proteins that facilitate formation of signaling networks. Predicting the PDZ domain's binding specificity was a part of the DREAM4 Peptide Recognition Domain challenge, the goal of which was to describe, as position weight matrices, the specificity profiles of five multi-mutant ERBB2IP-1 domains. We developed a method that derives multi-mutant binding preferences by generalizing the effects of single point mutations on the wild type domain's binding specificities. Our approach, trained on publicly available ERBB2IP-1 single-mutant phage display data, combined linear regression-based prediction for ligand positions whose specificity is determined by few PDZ positions, and single-mutant position weight matrix averaging for all other ligand columns. The success of our method as the winning entry of the DREAM4 competition, as well as its superior performance over a general PDZ-ligand binding model, demonstrates the advantages of training a model on a well-selected domain-specific data set