Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair

<p>Abstract</p> <p>Background</p> <p>Wound healing in horses is fraught with complications. Specifically, wounds on horse limbs often develop exuberant granulation tissue which behaves clinically like a benign tumor and resembles the human keloid in that the evolving scar is trapped in the proliferative phase of repair, leading to fibrosis. Clues gained from the study of over-scarring in horses should eventually lead to new insights into how to prevent unwanted scar formation in humans. cDNA fragments corresponding to <it>CTNNB1 </it>(coding for β-catenin) and <it>PECAM1</it>, genes potentially contributing to the proliferative phase of repair, were previously identified in a mRNA expression study as being up-regulated in 7 day wound biopsies from horses. The aim of the present study was to clone full-length equine <it>CTNNB1 </it>and <it>PECAM1 </it>cDNAs and to study the spatio-temporal expression of mRNAs and corresponding proteins during repair of body and limb wounds in a horse model.</p> <p>Results</p> <p>The temporal pattern of the two genes was similar; except for <it>CTNNB1 </it>in limb wounds, wounding caused up-regulation of mRNA which did not return to baseline by the end of the study. Relative over-expression of both <it>CTNNB1 </it>and <it>PECAM1 </it>mRNA was noted in body wounds compared to limb wounds. Immunostaining for both β-catenin and PECAM1 was principally observed in endothelial cells and fibroblasts and was especially pronounced in wounds having developed exuberant granulation tissue.</p> <p>Conclusion</p> <p>This study is the first to characterize equine cDNA for <it>CTNNB1 </it>and <it>PECAM1 </it>and to document that these genes are expressed during wound repair in horses. It appears that β-catenin may be regulated in a post-transcriptional manner while PECAM1 might help thoracic wounds mount an efficient inflammatory response in contrast to what is observed in limb wounds. Furthermore, data from this study suggest that β-catenin and PECAM1 might interact to modulate endothelial cell and fibroblast proliferation during wound repair in the horse.</p

Personalized treatment of asthma: the importance of sex and gender differences

An individual's sex (nominally 'male' or 'female', based on biological attributes) and gender (a complex term, referring to socially constructed roles, behaviors, and expressions of identity) influences the clinical course of asthma in several ways. The physiological development of the lungs and effects of sex hormones may explain why more boys have asthma than girls, and post-puberty, more women have asthma than men. Female sex hormones have an impact throughout the lifespan and are associated with poor asthma control. Gender may influence exposure to asthma triggers, and sex and gender can influence the prevalence of comorbidities and interactions with healthcare professionals (HCPs). Despite widely reported sex and gender-based differences in asthma and asthma management, these issues are frequently not considered by HCPs. There is also inconsistency around use of 'sex' and 'gender' in scientific discourse, and research is needed to better define sex and gender-based differences and how they might interact to influence asthma outcomes. This review outlines the impact an individual's sex and gender can have on the pathogenesis, clinical course, diagnosis, treatment, and management of asthma

The Max b-HLH-LZ Can Transduce into Cells and Inhibit c-Myc Transcriptional Activities

The inhibition of the functions of c-Myc (endogenous and oncogenic) was recently shown to provide a spectacular therapeutic index in cancer mouse models, with complete tumor regression and minimal side-effects in normal tissues. This was achieved by the systemic and conditional expression of omomyc, the cDNA of a designed mutant of the b-HLH-LZ of c-Myc named Omomyc. The overall mode of action of Omomyc consists in the sequestration of Max and the concomitant competition of the Omomyc/Max complex with the endogenous c-Myc/Max heterodimer. This leads to the inhibition of the transactivation of Myc target genes involved in proliferation and metabolism. While this body of work has provided extraordinary insights to guide the future development of new cancer therapies that target c-Myc, Omomyc itself is not a therapeutic agent. In this context, we sought to exploit the use of a b-HLH-LZ to inhibit c-Myc in a cancer cell line in a more direct fashion. We demonstrate that the b-HLH-LZ domain of Max (Max*) behaves as a bona fide protein transduction domain (PTD) that can efficiently transduce across cellular membrane via through endocytosis and translocate to the nucleus. In addition, we show that the treatment of HeLa cells with Max* leads to a reduction of metabolism and proliferation rate. Accordingly, we observe a decrease of the population of HeLa cells in S phase, an accumulation in G1/G0 and the induction of apoptosis. In agreement with these phenotypic changes, we show by q-RT-PCR that the treatment of HeLa cells with Max* leads to the activation of the transcription c-Myc repressed genes as well as the repression of the expression of c-Myc activated genes. In addition to the novel discovery that the Max b-HLH-LZ is a PTD, our findings open up new avenues and strategies for the direct inhibition of c-Myc with b-HLH-LZ analogs

Topology of molecular machines of the endoplasmic reticulum: a compilation of proteomics and cytological data

The endoplasmic reticulum (ER) is a key organelle of the secretion pathway involved in the synthesis of both proteins and lipids destined for multiple sites within and without the cell. The ER functions to both co- and post-translationally modify newly synthesized proteins and lipids and sort them for housekeeping within the ER and for transport to their sites of function away from the ER. In addition, the ER is involved in the metabolism and degradation of specific xenobiotics and endogenous biosynthetic products. A variety of proteomics studies have been reported on different subcompartments of the ER providing an ER protein dictionary with new data being made available on many protein complexes of relevance to the biology of the ER including the ribosome, the translocon, coatomer proteins, cytoskeletal proteins, folding proteins, the antigen-processing machinery, signaling proteins and proteins involved in membrane traffic. This review examines proteomics and cytological data in support of the presence of specific molecular machines at specific sites or subcompartments of the ER

Integrating social science into conservation planning

A growing body of literature has highlighted the value of social science for conservation, yet the diverse approaches of the social sciences are still inconsistently incorporated in conservation initiatives. Building greater capacity for social science integration in conservation requires frameworks and case studies that provide concrete guidance and specific examples. To address this need, we have developed a framework aimed at expanding the role for social science in formal conservation planning processes. Our framework illustrates multiple ways in which social science research can contribute to four stages of such processes: 1) defining the problem and project team; 2) defining goals; 3) identifying impact pathways and designing interventions; and 4) developing and evaluating indicators of success (or failure). We then present a timely case study of wolf reintroduction in Colorado, U.S.A., to demonstrate the opportunities, challenges, and complexities of applying our framework in practice