Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA

The rat beta-tropomyosin gene encodes two isoforms, termed skeletal muscle beta-tropomyosin and fibroblast last tropomyosim 1 (TM-1), via an alternative RNA processing mechanism. The gene contains 11 exons. Exons 1-5 and exons 8 and 9 are common to all mRNAs expressed from the gene. Exons 6 and 11 are used in fibroblasts, as well as smooth muscle, whereas exons 7 and 10 are used only in skeletal muscle. In the present studies we focused on the mutually exclusive internal alternative splice choice involving exon 6 (fibroblast-type splice) and exon 7 (skeletal muscle-type splice). We have identified two distinct elements in the intron, upstream of exon 7, involved in splice site selection. The first element is comprised of a polypyrimidine tract located 89-143 nucleotides upstream of the 3' splice site, which specifies the location of the lariat branchpoints used, 144-153 nucleotides upstream of exon 7. The 3' splice site AG dinucleotide has no role in selection of these branchpoints. The second element is comprised of intron sequences located between the polypyrimidine tract and the 3' splice site of exon 7. It contains an important determinant in alternative splice site selection, because deletion of these sequences results in the use of the skeletal muscle-specific exon in nonmuscle cells. We propose that the use of lariat branchpoints located far upstream from a 3' splice site may be a general feature of some alternatively excised introns, reflecting the presence of regulatory sequences located between the lariat branch site and the 3' splice site. The data also indicate that alternative splicing of the rat beta-tropomyosin gene is regulated by a somewhat different mechanism from that described for rat alpha-tropomyosin gene and the transformer-2 gene of Drosophila melanogaster

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Vaginal metastasis of a Ewing sarcoma five years after resection of the primary tumor

A 35-year-old female presented with pain and swelling of the distal left radius. A diagnosis of Ewing sarcoma was made and she underwent neoadjuvant chemotherapy and surgery. Macroscopic viable areas remained on the map of the surgical specimen; as such, she was classified as a poor responder and received high dose adjuvant chemotherapy. She remained disease-free for five years, until age 40. A vaginal polyp was then detected during a routine gynaecologic examination. It was removed and histopathology revealed metastatic Ewing sarcoma

Feeding Concentrate Formulated With Native Irish Feed Ingredients and a Low Crude Protein Content to Grazing Dairy Cows Has No Effect on Milk Production or Milk Composition

Improving nitrogen use efficiency (NUE) and feeding native feed ingredients offers potential to improve the environmental sustainability of dairy production. However, improving NUE is a key challenge in grass-based systems due to high crude protein (CP) levels in grass and low nitrogen retention by dairy cows. In addition, concentrate feed typically contains imported feed ingredients which contribute to increased carbon footprint. Therefore, the objective of this study was to investigate the effect of concentrate CP level and ingredient source on milk production and composition. Forty-two mixed-parity Holstein-Friesian cows were blocked on parity and balanced on days in milk (DIM), milk production, BCS and Economic Breeding Index (EBI; n=14). Cows grazed full time and were offered a basal diet of perennial ryegrass pasture (average 17 kg DM/cow/day) and fed one of three concentrate supplements at varying levels according to DIM during the main grazing season (153 days). The concentrate treatments (T) were: T1) 14% CP concentrate formulated with non-native ingredients, T2) 12% CP concentrate formulated with non-native ingredients or T3) 12% CP concentrate formulated with native ingredients. Reducing the CP level or formulating with native feed ingredients did not alter milk or milk solids yield (T1: 25.7 kg/day, 2.11 kg/day; T2: 25.3 kg/day, 2.06 kg/day; T3: 24.9 kg/day, 2.01 kg/day respectively). Similarly, no effect of treatment was observed for milk fat or protein percentage (T1: 4.40 %, 3.66 %; T2: 4.44 %, 3.64 %; T3: 4.37 %, 3.66 %, respectively). The results of this study highlight that the sustainability of grass-based dairy may be improved by using a low concentrate CP content (12%) in addition to offering concentrate feed based on native feed ingredients which can result in similar performance to that of dairy cows offered a 14% CP concentrate or a concentrate based on imported ingredients respectively

Corridors of barchan dunes: stability and size selection

Barchans are crescentic dunes propagating on a solid ground. They form dune fields in the shape of elongated corridors in which the size and spacing between dunes are rather well selected. We show that even very realistic models for solitary dunes do not reproduce these corridors. Instead, two instabilities take place. First, barchans receive a sand flux at their back proportional to their width while the sand escapes only from their horns. Large dunes proportionally capture more than they loose sand, while the situation is reversed for small ones: therefore, solitary dunes cannot remain in a steady state. Second, the propagation speed of dunes decreases with the size of the dune: this leads -- through the collision process -- to a coarsening of barchan fields. We show that these phenomena are not specific to the model, but result from general and robust mechanisms. The length scales needed for these instabilities to develop are derived and discussed. They turn out to be much smaller than the dune field length. As a conclusion, there should exist further - yet unknown - mechanisms regulating and selecting the size of dunes.Comment: 13 pages, 13 figures. New version resubmitted to Phys. Rev. E. Pictures of better quality available on reques

CME Evolution in the Structured Heliosphere and Effects at Earth and Mars During Solar Minimum

The activity of the Sun alternates between a solar minimum and a solar maximum, the former corresponding to a period of "quieter" status of the heliosphere. During solar minimum, it is in principle more straightforward to follow eruptive events and solar wind structures from their birth at the Sun throughout their interplanetary journey. In this paper, we report analysis of the origin, evolution, and heliospheric impact of a series of solar transient events that took place during the second half of August 2018, i.e. in the midst of the late declining phase of Solar Cycle 24. In particular, we focus on two successive coronal mass ejections (CMEs) and a following high-speed stream (HSS) on their way towards Earth and Mars. We find that the first CME impacted both planets, whilst the second caused a strong magnetic storm at Earth and went on to miss Mars, which nevertheless experienced space weather effects from the stream interacting region (SIR) preceding the HSS. Analysis of remote-sensing and in-situ data supported by heliospheric modelling suggests that CME--HSS interaction resulted in the second CME rotating and deflecting in interplanetary space, highlighting that accurately reproducing the ambient solar wind is crucial even during "simpler" solar minimum periods. Lastly, we discuss the upstream solar wind conditions and transient structures responsible for driving space weather effects at Earth and Mars.Comment: 27 pages, 7 figures, 1 table, accepted for publication in Space Weathe

Salerno's model of DNA reanalysed: could solitons have biological significance?

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether ``breather'' solitons could play a role in the facilitated location of promoters by RNA polymerase. In an effective potential formalism, we find excellent correlation between potential minima and {\em Escherichia coli} promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while ``flat'' regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein ``particle'' about a bent DNA axis.Comment: Latex file 20 pages, 5 figures. Manuscript of paper to appear in J. Biol. Phys., accepted 02/09/0