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- Animal board invited review: advances in proteomics for animal and food sciencesPublication . Almeida, A. M.; Bassols, A.; Bendixen, E.; Bhide, M.; Ceciliani, F.; Cristobal, S.; Eckersall, P. D.; Hollung, K.; Lisacek, F.; Mazzucchelli, G.; McLaughlin, M.; Miller, I.; Nally, J. E.; Plowman, J.; Renaut, J.; Rodrigues, P.; Roncada, P.; Staric, J.; Turk, R.Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.
- Acute stroke with concomitant acute myocardial infarction: will you thrombolyse?Publication . Maciel, Rita; Palma, Raquel; Sousa, Pedro; Ferreira, Fatima; Nzwalo, HipólitoConcomitant occurrence of acute myocardial infarction (MI) and stroke is infrequently encountered in emergent patients. Acute MI within the previous 3 months is considered a relative contraindication for therapy with alteplase or intravenous tissue plasminogen activator (IV rtPA).1 The use of IV rtPA for stroke in patients with a recent MI is associated with an increased risk of cardiac rupture, secondary to breakdown of the existing fibrin clot within the necrotic myocardium and/or degradation of collagen2 . Whether it is appropriate to perform thrombolysis in an emergent patient with concomitant ischemic stroke and MI remains a matter for debate.
- Patterning in time and space: HoxB cluster gene expression in the developing chick embryoPublication . Gouveia, Analuce; Marcelino, Hugo M.; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P.The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space.
- Self-reported quality care for knee osteoarthritis: comparisons across Denmark, Norway, Portugal and the UKPublication . Osteras, N.; Jordan, K. P.; Clausen, B.; Cordeiro, C.; Dziedzic, K.; Edwards, J.; Gronhaug, G.; Higginbottom, A.; Lund, H.; Pacheco, G.; Pais, S.; Hagen, K. B.Objectives: To assess and compare patient perceived quality of osteoarthritis (OA) management in primary healthcare in Denmark, Norway, Portugal and the UK. Methods: Participants consulting with clinical signs and symptoms of knee OA were identified in 30 general practices and invited to complete a cross-sectional survey including quality indicators (QI) for OA care. A QI was considered as eligible if the participant had checked 'Yes' or 'No', and as achieved if the participant had checked 'Yes' to the indicator. The median percentage (with IQR and range) of eligible QIs achieved by country was determined and compared in negative binominal regression analysis. Achievement of individual QIs by country was determined and compared using logistic regression analyses. Results: A total of 354 participants self-reported QI achievement. The median percentage of eligible QIs achieved (checked 'Yes') was 48% (IQR 28%, 64%; range 0-100%) for the total sample with relatively similar medians across three of four countries. Achievement rates on individual QIs showed a large variation ranging from 11% (referral to services for losing weight) to 67% (information about the importance of exercise) with significant differences in achievement rates between the countries. Conclusions: The results indicated a potential for improvement in OA care in all four countries, but for somewhat different aspects of OA care. By exploring these differences and comparing healthcare services, ideas may be generated on how the quality might be improved across nations. Larger studies are needed to confirm and further explore the findings.
- Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriersPublication . Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Nevanlinna, Heli; Aittomaeki, Kristiina; van Os, Theo A. M.; Jensen, Uffe Birk; Meijers-Heijboer, Hanne E. J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P. G.; Rappaport, Christine; Hoogerbrugge, Nicoline; Arason, Adalgeir; Jonson, Lars; Ausems, Margreet G. E. M.; van der Baan, Frederieke H.; van Doorn, Helena C.; Collee, J. Margriet; Olah, Edith; Diez, Orland; Laitman, Yael; Blanco, Ignacio; Lazaro, Conxi; Lose, Felicity; Osorio, Ana; Kaulich, Daphne Geschwantler; Brunet, Joan; Giannini, Giuseppe; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Walker, Logan C.; Martinez-Bouzas, Cristina; Szabo, Csilla I.; Offit, Kenneth; von Wachenfeldt, Anna; Papi, Laura; Ehrencrona, Hans; Corines, Marina; Barwell, Julian; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Rhiem, Kerstin; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Martayan, Aline; Glendon, Gord; Tchatchou, Sandrine; Maia, Ana-Teresa; Walker, Lisa; Montagna, Marco; Benitez, Javier; Andrulis, Irene L.; Niederacher, Dieter; Askmalm, Marie Stenmark; Borg, Ake; Kuchenbaecker, Karoline B.; Tibiletti, Maria Grazia; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Conway, Edye E.; Izatt, Louise; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Steinemann, Doris; Matricardi, Laura; Radice, Paolo; Friedman, Eitan; Lubinski, Jan; Jakubowska, Anna; Blazer, Kathleen R.; Garcia, Encarna B. Gomez; Olopade, Olufunmilayo I.; Side, Lucy E.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Vratimos, Athanassios; Plendl, Hansjoerg; Arun, Banu K.; Porteous, Mary E.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Kennedy, M. John; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Fostira, Florentia; Buys, Saundra S.; Weitzel, Jeffrey N.; Janavicius, Ramunas; Kast, Karin; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Rogers, Mark T.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Arnold, Norbert; Garber, Judy E.; Ejlertsen, Bent; Feliubadalo, Lidia; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Ditsch, Nina; Mariette, Frederique; Fortuzzi, Stefano; Morrison, Patrick J.; Cybulski, Cezary; Platte, Radka; Viel, Alessandra; Jacobs, Lauren; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Gronwald, Jacek; Cook, Jackie; Tischkowitz, Marc; Varon-Mateeva, Raymonda; Robson, Mark E.; Wappenschmidt, Barbara; Adlard, Julian; Toland, Amanda Ewart; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Spurdle, Amanda B.; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Zhang, Liying; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Bojesen, Anders; Wang-Gohrke, Shan; Durda, Katarzyna; Engel, Christoph; Chen, Bowang; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Joseph, Vijai; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Jaworska-Bieniek, Katarzyna; Pedersen, Inge Sokilde; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Rookus, Matti A.; Boutry-Kryza, Nadia; Berger, Andreas; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Sukiennicki, Grzegorz; Mazoyer, Sylvie; Belotti, Muriel; Thomassen, Mads; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J.; Singer, Christian F.; Schmidt, MarjankaK.; de la Hoya, Miguel; Rantala, Johanna; Perez Segura, PedroBackground: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. (C)2014 AACR.
- Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulumPublication . Avezov, Edward; Konno, Tasuku; Zyryanova, Alisa; Chen, Weiyue; Laine, Romain; Crespillo-Casado, Ana; Melo, Eduardo; Ushioda, Ryo; Nagata, Kazuhiro; Kaminski, Clemens F.; Harding, Heather P.; Ron, DavidBackground: Endoplasmic reticulum (ER) lumenal protein thiol redox balance resists dramatic variation in unfolded protein load imposed by diverse physiological challenges including compromise in the key upstream oxidases. Lumenal calcium depletion, incurred during normal cell signaling, stands out as a notable exception to this resilience, promoting a rapid and reversible shift towards a more reducing poise. Calcium depletion induced ER redox alterations are relevant to physiological conditions associated with calcium signaling, such as the response of pancreatic cells to secretagogues and neuronal activity. The core components of the ER redox machinery are well characterized; however, the molecular basis for the calcium-depletion induced shift in redox balance is presently obscure. Results: In vitro, the core machinery for generating disulfides, consisting of ERO1 and the oxidizing protein disulfide isomerase, PDI1A, was indifferent to variation in calcium concentration within the physiological range. However, ER calcium depletion in vivo led to a selective 2.5-fold decline in PDI1A mobility, whereas the mobility of the reducing PDI family member, ERdj5 was unaffected. In vivo, fluorescence resonance energy transfer measurements revealed that declining PDI1A mobility correlated with formation of a complex with the abundant ER chaperone calreticulin, whose mobility was also inhibited by calcium depletion and the calcium depletion-mediated reductive shift was attenuated in cells lacking calreticulin. Measurements with purified proteins confirmed that the PDI1A-calreticulin complex dissociated as Ca2+ concentrations approached those normally found in the ER lumen ([Ca2+] K-0.5max = 190 mu M). Conclusions: Our findings suggest that selective sequestration of PDI1A in a calcium depletion-mediated complex with the abundant chaperone calreticulin attenuates the effective concentration of this major lumenal thiol oxidant, providing a plausible and simple mechanism for the observed shift in ER lumenal redox poise upon physiological calcium depletion.
- Vertical movement patterns and ontogenetic niche expansion in the Tiger Shark, Galeocerdo cuvierPublication . Afonso, Andre S.; Hazin, Fábio H. V.Sharks are top predators in many marine ecosystems and can impact community dynamics, yet many shark populations are undergoing severe declines primarily due to overfishing. Obtaining species-specific knowledge on shark spatial ecology is important to implement adequate management strategies for the effective conservation of these taxa. This is particularly relevant concerning highly-mobile species that use wide home ranges comprising coastal and oceanic habitats, such as tiger sharks, Galeocerdo cuvier. We deployed satellite tags in 20 juvenile tiger sharks off northeastern Brazil to assess the effect of intrinsic and extrinsic factors on depth and temperature usage. Sharks were tracked for a total of 1184 d and used waters up to 1112 m in depth. The minimum temperature recorded equaled 4 degrees C. All sharks had a clear preference for surface (< 5 m) waters but variability in depth usage was observed as some sharks used mostly shallow (< 60 m) waters whereas others made frequent incursions into greater depths. A diel behavioral shift was detected, with sharks spending considerably more time in surface (< 10 m) waters during the night. Moreover, a clear ontogenetic expansion in the vertical range of tiger shark habitat was observed, with generalized linear models estimating a similar to 4-fold increase in maximum diving depth from 150- to 300-cm size-classes. The time spent in the upper 5 m of the water column did not vary ontogenetically but shark size was the most important factor explaining the utilization of deeper water layers. Young-of-the-year tiger sharks seem to associate with shallow, neritic habitats but they progressively move into deeper oceanic habitats as they grow larger. Such an early plasticity in habitat use could endow tiger sharks with access to previously unavailable prey, thus contributing to a wider ecological niche.
- Effects of fishery protection on biometry and genetic structure of two target sea cucumber species from the Mediterranean SeaPublication . Gonzalez-Wangueemert, Mercedes; Valente, Sara; Aydin, MehmetSea cucumber fisheries are now occurring in most of the tropical areas of the world, having expanded from its origin in the central Indo-Pacific. Due to the overexploitation of these resources and the increasing demand from Asian countries, new target species from Mediterranean Sea and northeastern Atlantic Ocean are being caught. The fishery effects on biometry and genetic structure of two target species (Holothuria polii and H. tubulosa) from Turkey, were assessed. The heaviest and largest individuals of H. polii were found into the non-fishery area of Kusadasi, also showing the highest genetic diversity. Similar pattern was detected in H. tubulosa, but only the weight was significantly higher in the protected area. However, the observed differences on the fishery effects between species, could be explained considering the different percentage of catches (80% for H. polii and 20% for H. tubulosa).
- Ecological zonation of benthic foraminifera in the lower Guadiana Estuary (southeastern Portugal)Publication . Camacho, Sarita; Moura, Delminda; Connor, Simon; Scott, David; Boski, T.The present study analyzes the spatial distribution and seasonal distribution of live benthic foraminiferal communities in the estuary of Guadiana, the fourth largest river on the Iberian Peninsula, and establishes, through statistical analysis, their relationships with a series of environmental parameters. Forty-four superficial sediment samples were collected along distance-to-sea and elevation gradients in the winter and summer of 2010. Fifty-three foraminifera species were identified along the intertidal margins of the estuary. Foraminiferal distribution reflected seasonal variation of environmental factors, whose relative importance varied according to species tolerances. Elevation in relation to mean sea level appeared to be the most important parameter controlling foraminiferal distribution, probably because it combines the effects of a series of other variables (i.e. organic matter, sediment texture, pH and temperature). In the highest marsh areas, where environmental conditions approach survival thresholds, only some agglutinated species are able to survive. In the lower intertidal zone, where subaerial exposure is diminished and environmental conditions are generally less variable, more diverse faunas, mainly composed of calcareous species, prevail. During winter, when fluvial discharge peaks, agglutinated species represent more than 80% of the total individuals. In summer, when marine conditions prevail, calcareous species become more competitive, increase their densities and expand into higher marsh zones and estuarine upper reaches. In the estuary, three different foraminiferal assemblages are distinguished: i) Miliammina fusca assemblage, which dominates in unvegetated areas of the lower marsh and tidal flats of the mid-upper estuary; ii)Jadammina macrescens assemblage, which dominates in the highest marsh areas in the lower estuary; and iii) Ammonia aberdoveyensis assemblage, which dominates the areas of low marsh and tidal flats of the lower estuary. (C) 2014 Elsevier B.V. All rights reserved.
- Terapêutica da doença de AlzheimerPublication . Vieira, Catarina Isabel Andrade; Mota-Filipe, HélderA Doença de Alzheimer (DA) é uma doença devastadora que rouba as vidas das suas vítimas, deixando os membros familiares e os prestadores de cuidados perturbados e sem esperança. De acordo com o Relatório de 2013 da World Alzheimer, existem atualmente 36 milhões de doentes de Alzheimer, e é esperado que este número aumente para 66 milhões em 2030 e para 115 milhões em 2050. A DA é a forma mais comum de demência. É uma doença neurodegenerativa que se carateriza pela progressiva perda de células nervosas em várias zonas do cérebro, conduzindo a uma diminuição geral do tamanho do cérebro, o que se traduz por perda de memória. Na maioria dos casos afeta adultos com mais de 65 anos. A DA não tem uma etiologia completamente conhecida. Muitos investigadores acreditam que é uma doença multifatorial, resultante de um conjunto de fatores de risco ambientais e genéticos, que desencadeiam uma cascata fisiopatológica, iniciando um conjunto de alterações no cérebro vários anos antes do aparecimento dos sintomas. Estão a ser desenvolvidos esforços a nível mundial para identificar a etiologia da DA, encontrar a sua cura ou maneiras de prevenir ou minimizar o seu avanço. Atualmente esta doença não tem cura, pelo que, a terapêutica disponível tem como objetivo retardar e/ou estabilizar o declínio das capacidades cognitivas, funcionais e comportamentais, de modo a melhorar a qualidade de vida do doente, reduzir a carga dos cuidadores e retardar a institucionalização. Com este intuito são utilizadas duas classes de fármacos, os inibidores da acetilcolinesterase (donepezilo, galantamina e rivastigmina) e antagonistas dos recetores NMDA (memantina). Encontram-se atualmente em investigação fármacos modificadores da doença que têm como objetivo a erradicação de Aβ.