Gallus gallus NEU3 sialidase as model to study protein evolution mechanism based on rapid evolving loops

<p>Abstract</p> <p>Background</p> <p>Large surface loops contained within compact protein structures and not involved in catalytic process have been proposed as preferred regions for protein family evolution. These loops are subjected to lower sequence constraints and can evolve rapidly in novel structural variants. A good model to study this hypothesis is represented by sialidase enzymes. Indeed, the structure of sialidases is a β-propeller composed by anti-parallel β-sheets connected by loops that suit well with the rapid evolving loop hypothesis. These features prompted us to extend our studies on this protein family in birds, to get insights on the evolution of this class of glycohydrolases.</p> <p>Results</p> <p><it>Gallus gallus (Gg) </it>genome contains one <it>NEU3 </it>gene encoding a protein with a unique 188 amino acid sequence mainly constituted by a peptide motif repeated six times in tandem with no homology with any other known protein sequence. The repeat region is located at the same position as the roughly 80 amino acid loop characteristic of mammalian NEU4. Based on molecular modeling, all these sequences represent a connecting loop between the first two highly conserved β-strands of the fifth blade of the sialidase β-propeller. Moreover this loop is highly variable in sequence and size in NEU3 sialidases from other vertebrates. Finally, we found that the general enzymatic properties and subcellular localization of Gg NEU3 are not influenced by the deletion of the repeat sequence.</p> <p>Conclusion</p> <p>In this study we demonstrated that sialidase protein structure contains a surface loop, highly variable both in sequence and size, connecting two conserved β-sheets and emerging on the opposite site of the catalytic crevice. These data confirm that sialidase family can serve as suitable model for the study of the evolutionary process based on rapid evolving loops, which may had occurred in sialidases. Giving the peculiar organization of the loop region identified in Gg NEU3, this protein can be considered of particular interest in such evolutionary studies and to get deeper insights in sialidase evolution.</p

Characterization of the AP-1 μ1A and μ1B adaptins in zebrafish (Danio rerio)

Protein transport between the trans-Golgi network and endosomes is mediated by transport vesicles formed by the adaptor-protein complex AP-1, consisting of the adaptins γ1, β1, μ1, σ1. Mammalia express μ1A ubiquitously and isoform μ1B in polarized epithelia. Mouse γ1 or μ1A 'knock out's revealed that AP-1 is indispensable for embryonic development. We isolated μ1A and μ1B from Danio rerio. Analysis of μ1A and μ1B expression revealed tissue-specific expression for either one during embryogenesis and in adult tissues in contrast to their expression in mammalia. μ1B transcript was detected in organs of endodermal derivation and "knock-down" experiments gave rise to embryos defective in formation of intestine, liver, and pronephric ducts. Development ceased at 7-8 dpf. μ1B is not expressed in murine liver, indicating loss of μ1B expression and establishment of alternative sorting mechanisms during mammalian development

Comparação do impacto de anastomose torácica ou cervical no pós operatório de esofagogastrectomia - análise de 92 casos/ Comparison of the impact of thoracic or cervical anastomosis on postoperative esophagogastrectomy - analysis of 92 cases

A esofagectomia é o tratamento curativo do câncer de esôfago não metastático atualmente. Contudo ainda há falta de evidências fiéis que mostrem uma diferença significativa entre as técnicas cirúrgicas e permanece a controvérsia sobre a localização anatômica ideal da anastomose esofagogástrica, intratorácica ou cervical. O objetivo desse estudo foi avaliar a influência do local da anastomose, cervical ou torácica, nas complicações operatórias e mortalidade da esofagogastrectomia com linfadenectomia em dois campos

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

Purpose: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. Methods: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. Results: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001) but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean +/- standard deviation baseline central macular thickness (552 +/- 150 mu m) reduced significantly one month (322 +/- 127 mu m, P=0.0001) and three months (439 perpendicular to 179 mu m, P=0.01) after treatment. Conclusions: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements

Predictive Validity of the Three-Factor Model of Impulsivity for Risky Behaviors

Impulsivity is a multifaceted construct particularly relevant for understanding a wide variety of behaviors, especially risky behaviors. A recent conceptualization of impulsivity identifies three impulsivity factors—pervasive influence of feelings, feelings trigger action, and lack of follow-through—that have been shown to predict different behaviors. In this contribution, we examine the psychometric properties of an Italian version of such a three-factor model on a relatively large sample (N = 845). Moreover, on a subsample (n = 766) we determined whether specific dimensions of impulsivity are related to a series of risky behaviors, assessed 3 weeks later, by testing the predictive validity of the multidimensional inventory also in comparison with a standard measure of personality (HEXACO). An exploratory structural equation model confirmed the original 3-dimension structure and showed that the Italian adaptation has satisfactory psychometric properties. Convergent validity with the HEXACO dimensions was established. Furthermore, only the factors feelings trigger action and lack of follow-through, not pervasive influence of feelings, predicted risky behaviors. Findings provide a clear support to the 3-factor model of impulsivity and demonstrate its usefulness for a better comprehension of risky behaviors