Razor-thin dust layers in protoplanetary disks:Limits on the vertical shear instability

Context. Recent observations with the Atacama Large Millimeter Array (ALMA) have shown that the large dust aggregates observed at millimeter wavelengths settle to the midplane into a remarkably thin layer. This sets strong limits on the strength of the turbulence and other gas motions in these disks. Aims. We intend to find out if the geometric thinness of these layers is evidence against the vertical shear instability (VSI) operating in these disks. We aim to verify if a dust layer consisting of large enough dust aggregates could remain geometrically thin enough to be consistent with the latest observations of these dust layers, even if the disk is unstable to the VSI. If this is falsified, then the observed flatness of these dust layers proves that these disks are stable against the VSI, even out to the large radii at which these dust layers are observed. Methods. We performed hydrodynamic simulations of a protoplanetary disk with a locally isothermal equation of state, and let the VSI fully develop. We sprinkled dust particles with a given grain size at random positions near the midplane and followed their motion as they got stirred up by the VSI, assuming no feedback onto the gas. We repeated the experiment for different grain sizes and determined for which grain size the layer becomes thin enough to be consistent with ALMA observations. We then verified if, with these grain sizes, it is still possible (given the constraints of dust opacity and gravitational stability) to generate a moderately optically thick layer at millimeter wavelengths, as observations appear to indicate. Results. We found that even very large dust aggregates with Stokes numbers close to unity get stirred up to relatively large heights above the midplane by the VSI, which is in conflict with the observed geometric thinness. For grains so large that the Stokes number exceeds unity, the layer can be made to remain thin, but we show that it is hard to make dust layers optically thick at ALMA wavelengths (e.g., τ1.3mm ≳ 1) with such large dust aggregates. Conclusions. We conclude that protoplanetary disks with geometrically thin midplane dust layers cannot be VSI unstable, at least not down to the disk midplane. Explanations for the inhibition of the VSI out to several hundreds of au include a high dust-to-gas ratio of the midplane layer, a modest background turbulence, and/or a reduced dust-to-gas ratio of the small dust grains that are responsible for the radiative cooling of the disk. A reduction of small grains by a factor of between 10 and 100 is sufficient to quench the VSI. Such a reduction is plausible in dust growth models, and still consistent with observations at optical and infrared wavelengths

Deletion of the trpc4 gene and its role in simple and complex strategic learning

The TRPC4 ion channel is expressed extensively in corticolimbic and a subpopulation of midbrain dopamine neurons. While TRPC4 knockout (KO) rats exhibit reduced sociability and social exploration, little is known about the role of TRPC4 in motivation and learning. To identify a function for TRPC4 channels in learning processes  we tested TRPC4 KO and normal wild type (WT) rats. TRPC4 KO and WT rats exhibited no differences in Y-­maze learning or simple discrimination learning. Furthermore, on a more complex serial reversal shift task designed  to assess strategic learning where the reward and non-­reward cues were repeatedly reversed between training sessions both TRPC4 KO and WT rats   performed equally well. Finally, we found no   performance differences when using a conditional reversal shift task where a tone signals the reversal of reward and non-reward cues within sessions. These data suggest that although TRPC4 channels may play a role in social interaction/anxiety  they exert a minimal role in simple and complex strategic learning

Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture

Summary Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. Introduction The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. Methods Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. Results Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (−60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, −39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (−39%, −21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. Conclusions This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture

Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures

Characterization of L1 retrotransposition with high-throughput dual-luciferase assays

Recent studies employing genome-wide approaches have provided an unprecedented view of the scope of L1 activities on structural variations in the human genome, and further reinforced the role of L1s as one of the major driving forces behind human genome evolution. The rapid identification of novel L1 elements by these high-throughput approaches demands improved L1 functional assays. However, the existing assays use antibiotic selection markers or fluorescent proteins as reporters; neither is amenable to miniaturization. To increase assay sensitivity and throughput, we have developed a third generation assay by using dual-luciferase reporters, in which firefly luciferase is used as the retrotransposition indicator and Renilla luciferase is encoded on the same or separate plasmid for normalization. This novel assay is highly sensitive and has a broad dynamic range. Quantitative data with high signal-to-noise ratios can be obtained from 24- up to 96-well plates in 2–4 days after transfection. Using the dual-luciferase assays, we have characterized profiles of retrotransposition by various human and mouse L1 elements, and detailed the kinetics of L1 retrotransposition in cultured cells. Its high-throughput and short assay timeframe make it well suited for routine tests as well as large-scale screening efforts

Spontaneous coronary artery dissection presenting as an ischaemic stroke in a middle-aged man with anti-cardiolipin antibodies: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cerebrovascular disease is a major cause of mortality and morbidity worldwide. Ischemic stroke is the most common manifestation, encompassing a wide variety of causative mechanisms. We present the case of a middle-aged male patient with spontaneous coronary artery dissection in the presence of anti-cardiolipin antibodies, leading to left ventricular thrombus and presenting with stroke.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian man presented with dysarthria and right-sided weakness. There was a history of chest pain with autonomic symptoms four days earlier. Examination revealed right-sided hemiparesis. Electrocardiogram showed sinus rhythm with anterior Q waves. Magnetic resonance imaging of the brain showed large left parietal and smaller multiple cerebral infarcts. Echocardiogram showed anterior wall and apical akinesis with a large mural thrombus. Anti-cardiolipin antibodies immunoglobulin G and immunoglobulin M were strongly positive. Coronary angiography showed dissection of the mid left anterior descending artery with normal flow down the distal vessel. He was treated conservatively with anticoagulation and secondary prevention. He was in good health when seen in clinic four months later.</p> <p>Conclusion</p> <p>We highlight the importance of a comprehensive approach at obtaining the correct diagnosis, input of different specialities and the fact that the presence of anti-cardiolipin antibodies is associated with coronary artery dissection in a middle-aged male patient whose presentation was stroke.</p

A single amino acid substitution in ORF1 dramatically decreases L1 retrotransposition and provides insight into nucleic acid chaperone activity

L1 is a ubiquitous interspersed repeated sequence in mammals that achieved its high copy number by autonomous retrotransposition. Individual L1 elements within a genome differ in sequence and retrotransposition activity. Retrotransposition requires two L1-encoded proteins, ORF1p and ORF2p. Chimeric elements were used to map a 15-fold difference in retrotransposition efficiency between two L1 variants from the mouse genome, TFC and TFspa, to a single amino acid substitution in ORF1p, D159H. The steady-state levels of L1 RNA and protein do not differ significantly between these two elements, yet new insertions are detected earlier and at higher frequency in TFC, indicating that it converts expressed L1 intermediates more effectively into new insertions. The two ORF1 proteins were purified and their nucleic acid binding and chaperone activities were examined in vitro. Although the RNA and DNA oligonucleotide binding affinities of these two ORF1 proteins were largely indistinguishable, D159 was significantly more effective as a nucleic acid chaperone than H159. These findings support a requirement for ORF1p nucleic acid chaperone activity at a late step during L1 retrotransposition, extend the region of ORF1p that is known to be critical for its functional interactions with nucleic acids, and enhance understanding of nucleic acid chaperone activity