Structural and molecular characteristics of axons in the long head of the biceps tendon

The innervation of the long head of the biceps tendon (LHBT) is not sufficiently documented. This is a drawback since pathologies of the LHBT are a major source of shoulder pain. Thus, the study aimed to characterize structurally and molecularly nervous elements of the LHBT. The proximal part of 11 LHBTs was harvested intraoperatively. There were 8 female and 3 male specimens. Age ranged from 66 to 86 years. For structural analyses, nervous elements were viewed in the transmission electron microscope. For molecular characterization, we used general neuronal markers including antibodies against neurofilament and protein gene product 9.5 (PGP9.5) as well as specific neuronal markers including antibodies against myelin basic protein (MBP), calcitonin gene-related product (CGRP), substance P (SP), tyrosine hydroxylase (TH), and growth-associated protein 43 (GAP43). Anti-neurofilament and anti-PGP9.5 visualized the overall innervation. Anti-MBP visualized myelination, anti-CGRP and anti-SP nociceptive fibers, anti-TH sympathetic nerve fibers, and anti-GAP43 nerve fibers during development and regeneration. Immunolabeled sections were analyzed in the confocal laser scanning microscope. We show that the LHBT contains unmyelinated as well as myelinated nerve fibers which group in nerve fascicles and follow blood vessels. Manny myelinated and unmyelinated axons exhibit molecular features of nociceptive nerve fibers. Another subpopulation of unmyelinated axons exhibits molecular characteristics of sympathetic nerve fibers. Unmyelinated sympathetic fibers and unmyelinated nociceptive fibers express proteins that are found during development and regeneration. Present findings support the hypothesis that ingrowth of nociceptive fibers are the source of chronic tendon pain

Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis

Local environment of optically active Nd3 + ions in the ultratransparent BaMgF 4 ferroelectric crystal

A comprehensive study of the site location of Nd3 + ions in the BaMgF 4 ultratransparent ferroelectric crystal is presented. By combining different low-temperature optical spectroscopies and electron paramagnetic resonance, the crystal field energy levels of Nd3 + ions and the gyromagnetic factors are experimentally determined. These results are employed to perform the crystal field analysis of Nd3 + ions considering a Cs point symmetry. The crystal field calculation yields a small root-mean-square deviation of 18 cm -1 and reveals a large crystal field strength (621 cm -1), verifying the assignment of the Ba2 + cationic site as the location for Nd3 + ions in this fluoride host. The results suggest a slight displacement of Nd3 + from the barium regular site with a rearrangement of the fluorine ions around it. The work gives a deep insight into the properties of the Nd3 +-doped BaMgF 4 crystal, a ferroelectric widely ultra-transparent material with potential applications as optical device operating in the Vacuum Ultraviolet-Ultraviolet and midinfrared spectral regionsThis work has been supported by the Spanish Ministry of Science under projects MAT2010-17443, MAT2010-21270-C04-02, Consolider-Ingenio MALTA CSD 2007-0045, and Comunidad Autonoma de Madrid under Grant 2009/MAT-175

Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues

Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an "RNA gain of function" hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis

Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction

Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression. We developed and tested the ability of an oligonucleotide, composed of 2'-O-methyl modified bases on a phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c miRNA binding, thereby upregulating utrophin expression and improving the dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides (SBOs) for 1 month in the mdx mouse model for DMD, led to increased utrophin expression along with improved muscle histology, decreased fibrosis and increased specific force. The functional improvement of dystrophic muscle achieved using let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for DMD

Non-Decarboxylative Ruthenium-Catalyzed Rearrangement of 4-Alkylidene-isoxazol-5-ones to Pyrazole- and Isoxazole-4-carboxylic Acids

Treatment of 4-(2-hydroaminoalkylidenyl)- and 4-(2-hydroxyalkylidenyl)-substituted isoxazol-5(4H)-ones with catalytic amounts of [RuCl2(p-cymene)]2, without any additive, afforded pyrazole- and isoxazole-4-carboxylic acids, respectively. The presence of an intramolecular H-bond in these substrates was the key to divert the classical mechanism toward a ring-opening non-decarboxylative path that is expected to generate a vinyl Ru-nitrenoid intermediate, the cyclization of which affords the rearranged products. A gram scale protocol demonstrated the synthetic applicability of this transformation

Ruthenium-Catalyzed Decarboxylative Rearrangement of 4-Alkenyl-isoxazol-5-ones to Pyrrole Derivatives

Easily accessible isoxazol-5(4H)-ones are useful precursors of heterocycles. In this context, we report the ruthenium-catalyzed transformation of 4-alkenyl-substituted isoxazol-5-ones to afford 1H-pyrrole derivatives. The operative conditions were proven to be effective also on cyclohexane-fused isoxazolones giving 4,5,6,7-tetrahydroindoles. The reactions, which allow for access to tri-and tetra-substituted pyrroles in moderate to high yields, occur through decarboxylative ring-opening/ring-closure involving C-H functionalization of the alkenyl moiety

ENFERMERÍA: CANALIZACIONES PERIFÉRICAS, ATENCIÓN, CUIDADOS, MANTENIMIENTO Y COMPLICACIONES.

The channelling of the vein tract is one of the techniques realized by the infirmary personnel that has mayor incidence in the patients. In our Hospital with a number of unrgencies between 500-600, it is confirmed that this technic is te most efficacious. In the casuality Deparment, with a personnel of 78-80 nurses, there is a considerable number of personnel, moved from other services or from new incorporation to the personnel. Students of the third year realize practises in the service. The objective of our study is to make bibliographic revision and to revise the different cattegories of new catheters incorporated to the service, all this with our personal experience with the purpose of update our knowledge to realize a good practise in the vein channelling. At the same time, make some recommendations in the possible complications that may occur.La canalización de vías venosas es una de las técnicas realizadas por el personal de enfermería que mayor incidencia presenta sobre los pacientes. En nuestro hospital, con un número de urgencias diarias que oscila entre 500-600, se confirma que la técnica de más incidencia es la canalización venosa. En nuestro Servicio de urgencias, con una plantilla de 78 enfermeros/as, hay un número considerable de enfermeros/as de nueva incorporación en la plantilla fija, enfermeros/as desplazados de otros servicios. También estudiantes de tercer curso de enfermería que realizan sus prácticas en el Servicio. El objetivo de nuestro estudio constituye en hacer una revisión bibliográfica, revisar las distintas modalidades de nuevos catéteres incorporados al Servicio, todo ello acompañado de nuestra experiencia personal con la finalidad de actualizar nuestros conocimientos para la realización de una buena práctica en las canalizaciones venosas. Al mismo tiempo hacer una serie de recomendaciones en los cuidados de cada una de las posibles complicaciones que pueden presentarse