Inhibition of Immune Synapse by Altered Dendritic Cell Actin Distribution: A New Pathway of Mesenchymal Stem Cell Immune Regulation

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Elastic properties of grafted microtubules

We use single-particle tracking to study the elastic properties of single microtubules grafted to a substrate. Thermal fluctuations of the free microtubule's end are recorded, in order to measure position distribution functions from which we calculate the persistence length of microtubules with contour lengths between 2.6 and 48 micrometers. We find the persistence length to vary by more than a factor of 20 over the total range of contour lengths. Our results support the hypothesis that shearing between protofilaments contributes significantly to the mechanics of microtubules.Comment: 9 pages, 3 figure

Met exon 14 skipping: A case study for the detection of genetic variants in cancer driver genes by deep learning

Background: Disruption of alternative splicing (AS) is frequently observed in cancer and might represent an important signature for tumor progression and therapy. Exon skipping (ES) represents one of the most frequent AS events, and in non-small cell lung cancer (NSCLC) MET exon 14 skipping was shown to be targetable. Methods: We constructed neural networks (NN/CNN) specifically designed to detect MET exon 14 skipping events using RNAseq data. Furthermore, for discovery purposes we also developed a sparsely connected autoencoder to identify uncharacterized MET isoforms. Results: The neural networks had a Met exon 14 skipping detection rate greater than 94% when tested on a manually curated set of 690 TCGA bronchus and lung samples. When globally applied to 2605 TCGA samples, we observed that the majority of false positives was characterized by a blurry coverage of exon 14, but interestingly they share a common coverage peak in the second intron and we speculate that this event could be the transcription signature of a LINE1 (Long Interspersed Nuclear Element 1)-MET (Mesenchymal Epithelial Transition receptor tyrosine kinase) fusion. Conclusions: Taken together, our results indicate that neural networks can be an effective tool to provide a quick classification of pathological transcription events, and sparsely connected autoencoders could represent the basis for the development of an effective discovery tool

Sialic acids and hyaluronan expression in the renal tubulointerstitial space of rat in an experimental sepsis model

Sialic acids and hyaluronan play important roles in maintaining structure and functionality of the kidney tubulointerstitial space. In several investigations, performed on some renal pathologies, morpho-functional changes of the tubulointerstitial space showed correlation with altered expression of these anionic components; no data are available on the expression of these molecules in this space during sepsis. Therefore, the aim of this study was to evaluate the expression of sialic acids and hyaluronan in the renal tubulointerstitial space in the early stages of an experimental animal model of polymicrobial sepsis. Experiments were performed on adult male rats assigned to two groups: 1) sham-operated (n=20); 2) Caecal Ligation and Puncture (CLP) (clinically model of polymicrobial infection that mimics human sepsis) (n=25). The groups were divided into 3 subgroups related to 3 time points after CLP or sham-operated: t1=0 h, t2=3 h and t3=7 h. For evidence of sepsis TNF-α plasma level was measured and microbiology of peritoneal fluid was examined with bacteriologic techniques. Urinary protein levels were measured to test the renal functional damage. Kidney samples of each group were processed to analyse the morphology, sialic acids expression, by using lectin histochemistry, and hyaluronan expression, by using immunohistochemistry. The results showed that plasma TNF-α level significantly increased after CLP induction when compared to sham-operated animals. Bacteriologic techniques revealed a polymicrobial infection after CLP. The proteinuria was significantly increased in CLP group. Morphological changes, such as edema and epithelial lesions, were observed in the tubulointerstitium space in CLP group. Lectin histochemistry showed decrease of sialic acids in the tubular wall of septic rats with respect to the control ones. The largest amount of acetylated sialic acid was evidenced in the sepsis group. Immunohistochemistry demonstrated hyaluronan presence only in the medullary interstitium in the control group; in the septic rats hyaluronan appeared also in the cortical interstitium and tubular wall. The findings indicate the existence of a correlation between sialic acids and hyaluronan altered expression and morpho-functional changes in the kidney tubulointerstitial space during sepsis. In addition, an important role of these anionic molecules in protection/ defence and repairing processes may be suggested

Convergent and parallel evolution in life habit of the scallops (Bivalvia: Pectinidae)

<p>Abstract</p> <p>Background</p> <p>We employed a phylogenetic framework to identify patterns of life habit evolution in the marine bivalve family Pectinidae. Specifically, we examined the number of independent origins of each life habit and distinguished between convergent and parallel trajectories of life habit evolution using ancestral state estimation. We also investigated whether ancestral character states influence the frequency or type of evolutionary trajectories.</p> <p>Results</p> <p>We determined that temporary attachment to substrata by byssal threads is the most likely ancestral condition for the Pectinidae, with subsequent transitions to the five remaining habit types. Nearly all transitions between life habit classes were repeated in our phylogeny and the majority of these transitions were the result of parallel evolution from byssate ancestors. Convergent evolution also occurred within the Pectinidae and produced two additional gliding clades and two recessing lineages. Furthermore, our analysis indicates that byssal attaching gave rise to significantly more of the transitions than any other life habit and that the cementing and nestling classes are only represented as evolutionary outcomes in our phylogeny, never as progenitor states.</p> <p>Conclusions</p> <p>Collectively, our results illustrate that both convergence and parallelism generated repeated life habit states in the scallops. Bias in the types of habit transitions observed may indicate constraints due to physical or ontogenetic limitations of particular phenotypes.</p

ALTERATIONS OF THE CORTICO-CORTICAL NETWORK IN SENSORI-MOTOR AREAS OF DYSTROPHIN DEFICIENT MICE

The dystrophin defective mdx mouse, acknowledged model of Duchenne Muscular Dystrophy (DMD), bears outstanding alterations of the cortical architecture, that could be responsible for the cognitive impairment often accompanying this pathological condition. Using a retrograde tract tracing technique to label neurons in Golgi-like fashion, we investigated the fine anatomical organization of associative cortico-cortical projections in mdx mice. While the absolute number of associative pyramidal neurons was significantly higher in mdx than in control animals, the ratio between the number of supra- and infragranular cortico-cortical cells was substantially unmodified. Basal dendrites of layer 2/3 pyramidal neurons displayed longer terminal branches in mdx compared to controls. Finally, the density of dendritic spines was significantly lower in mdx animals. The anomalies of associative cortico-cortical projections provide potential groundwork on the neurobiological bases of cognitive involvement in DMD and value the role of cortical microcircuitry alterations as possible source of interference with peripheral motor impairment