Overload and neovascularization of shoulder tendons in volleyball players

ABSTRACT: BACKGROUND: In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the rotator cuff tendons by oximetry. RESULTS: No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) middle hitters (53.7%), opposite hitters (55.5%) and libero players (54.4%) (p<0.05), whereas there was no difference in players with the role of setter (56.2%) (p>0.05). CONCLUSIONS: The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles.     

Multiple response optimization of alkaline pretreatment of sisal fiber (Agave sisalana) assisted by ultrasound

A procedure for the alkaline pretreatment of sisal fiber assisted by ultrasound was optimized to obtain a higher solubilization of hemicellulose and the removal of lignin with cellulose fraction maintenance. A full factorial design 2³ was used for the evaluation of the effects of the variables (sonication time, NaOH concentration, and sonication amplitude) on the pretreatment. The optimal values for the variables using the Doehlert matrix for the sonication time, NaOH concentration, and sonication amplitude were 27 min, 4.1% (m/v), and 50%, respectively. The X-ray diffractometry and scanning electron microscopy analyses, after pretreatment, showed changes in chemical structure and morphology due to the removal of 82% of hemicellulose and 86% of lignin from sisal fiber. The soft reaction conditions and relatively short times demonstrated the effectiveness of the combined action of ultrasound with alkaline pretreatment to improve the accessibility to cellulose in this important step of the ethanol production process from biomass.     

Levels of some enzymes acting on DNA in xeroderma pigmentosum

We have determined the levels of DNA polymerase, DNA ligase, a DNase acting on single-stranded DNA, an endonuclease making single-strand breaks in double - stranded DNA and polynucleotide kinase in fibroblasts obtained from nine normal persons and from nine patients with Xeroderma Pigmentosum; the pathological lines belong to the different described clinical forms and to the three different complementation groups described so far. All the enzymes are present in the normal lines and in the Xeroderma lines. The levels are quite variable, but the values obtained in the pathological lines lie within the ones observed in the normal population.     

Sensitivity of tumor cells towards CIGB‐300 anticancer peptide relies on its nucleolar localization

CIGB‐300 is a novel anticancer peptide that impairs the casein kinase 2‐mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB‐300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB‐300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB‐300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB‐300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB‐300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull‐down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB‐300‐treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB‐300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide‐based drug should entail its more efficient intracellular delivery at such subcellular localization. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

dNTP metabolism links mechanical cues and YAP/TAZ to cell growth and oncogene‐induced senescence

YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of cancer growth. How these factors control proliferation remains poorly defined. Here, we found that YAP/TAZ directly regulate expression of key enzymes involved in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer cells. Regulation of deoxynucleotide metabolism is required for YAP‐induced cell growth and underlies the resistance of YAP‐addicted cells to chemotherapeutics targeting dNTP synthesis. During RAS‐induced senescence, YAP/TAZ bypass RAS‐mediated inhibition of nucleotide metabolism and control senescence. Endogenous YAP/TAZ targets and signatures are inhibited by RAS/MEK1 during senescence, and depletion of YAP/TAZ is sufficient to cause senescence‐associated phenotypes, suggesting a role for YAP/TAZ in suppression of senescence. Finally, mechanical cues, such as ECM stiffness and cell geometry, regulate senescence in a YAP‐dependent manner. This study indicates that YAP/TAZ couples cell proliferation with a metabolism suited for DNA replication and facilitates escape from oncogene‐induced senescence. We speculate that this activity might be relevant during the initial phases of tumour progression or during experimental stem cell reprogramming induced by YAP.