Universidad de León

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal individuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research.

OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. ANIMALS: 6 healthy adult goats. PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.

An efficient system for genetic modification and large-scale cloning of cattle is of importance for agriculture, biotechnology, and human medicine. Here, actively dividing fetal fibroblasts were genetically modified with a marker gene, a clonal line was selected, and the cells were fused to enucleated mature oocytes. Out of 28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic calves were generated. Furthermore, the life-span of near senescent fibroblasts could be extended by nuclear transfer, as indicated by population doublings in fibroblast lines derived from a 40-day-old fetal clone. With the ability to extend the life-span of these primary cultured cells, this system would be useful for inducing complex genetic modifications in cattle.

Abstract Dominance by cyanobacteria hampers human use of lakes and reservoirs worldwide. Previous studies indicate that excessive nutrient loading and warmer conditions promote dominance by cyanobacteria, but evidence from global scale field data has so far been scarce. Our analysis, based on a study of 143 lakes along a latitudinal transect ranging from subarctic Europe to southern South America, shows that although warmer climates do not result in higher overall phytoplankton biomass, the percentage of the total phytoplankton biovolume attributable to cyanobacteria increases steeply with temperature. Our results also reveal that the percent cyanobacteria is greater in lakes with high rates of light absorption. This points to a positive feedback because restriction of light availability is often a consequence of high phytoplankton biovolume, which in turn may be driven by nutrient loading. Our results indicate a synergistic effect of nutrients and climate. The implications are that in a future warmer climate, nutrient concentrations may have to be reduced substantially from present values in many lakes if cyanobacterial dominance is to be controlled.

People feel they understand complex phenomena with far greater precision, coherence, and depth than they really do; they are subject to an illusion-an illusion of explanatory depth. The illusion is far stronger for explanatory knowledge than many other kinds of knowledge, such as that for facts, procedures or narratives. The illusion for explanatory knowledge is most robust where the environment supports real-time explanations with visible mechanisms. We demonstrate the illusion of depth with explanatory knowledge in Studies 1-6. Then we show differences in overconfidence about knowledge across different knowledge domains in Studies 7-10. Finally, we explore the mechanisms behind the initial confidence and behind overconfidence in Studies 11 and 12. Implications for the roles of intuitive theories in models of concepts and cognition are discussed.

Effects of 6 mo of heavy-resistance training combined with explosive exercises on neural activation of the agonist and antagonist leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris, as well as maximal and explosive strength were examined in 10 middle-aged men (M40; 42 +/- 2 yr), 11 middle-aged women (W40; 39 +/- 3 yr), 11 elderly men (M70; 72 +/- 3 yr) and 10 elderly women (W70; 67 +/- 3 yr). Maximal and explosive strength remained unaltered during a 1-mo control period with no strength training. After the 6 mo of training, maximal isometric and dynamic leg-extension strength increased by 36 +/- 4 and 22 +/- 2% (P < 0. 001) in M40, by 36 +/- 3 and 21 +/- 3% (P < 0.001) in M70, by 66 +/- 9 and 34 +/- 4% (P < 0.001) in W40, and by 57 +/- 10 and 30 +/- 3% (P < 0.001) in W70, respectively. All groups showed large increases (P < 0.05-0.001) in the maximum integrated EMGs (iEMGs) of the agonist vastus lateralis and medialis. Significant (P < 0.05-0.001) increases occurred in the maximal rate of isometric force production and in a squat jump that were accompanied with increased (P < 0.05-0. 01) iEMGs of the leg extensors. The iEMG of the antagonist biceps femoris muscle during the maximal isometric leg extension decreased in both M70 (from 24 +/- 6 to 21 +/- 6%; P < 0.05) and in W70 (from 31 +/- 9 to 24 +/- 4%; P < 0.05) to the same level as recorded for M40 and W40. The CSA of the quadriceps femoris increased in M40 by 5% (P < 0.05), in W40 by 9% (P < 0.01), in W70 by 6% (P < 0.05), and in M70 by 2% (not significant). Great training-induced gains in maximal and explosive strength in both middle-aged and elderly subjects were accompanied by large increases in the voluntary activation of the agonists, with significant reductions in the antagonist coactivation in the elderly subjects. Because the enlargements in the muscle CSAs in both middle-aged and elderly subjects were much smaller in magnitude, neural adaptations seem to play a greater role in explaining strength and power gains during the present strength-training protocol.

Melatonin is a highly evolutionary conserved endogenous molecule that is mainly produced by the pineal gland, but also by other nonendocrine organs, of most mammals including man. In the recent years, a variety of anti-inflammatory and antioxidant effects have been observed when melatonin is applied exogenously under both in vivo and in vitro conditions. A number of studies suggest that this indole may exert its anti-inflammatory effects through the regulation of different molecular pathways. It has been documented that melatonin inhibits the expression of the isoforms of inducible nitric oxide synthase and cyclooxygenase and limits the production of excessive amounts of nitric oxide, prostanoids, and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines, and adhesion molecules. Melatonin's anti-inflammatory effects are related to the modulation of a number of transcription factors such as nuclear factor kappa B, hypoxia-inducible factor, nuclear factor erythroid 2-related factor 2, and others. Melatonin's effects on the DNA-binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen-activated protein kinases. This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole's anti-inflammatory activity. Although there are a numerous published reports that have analyzed melatonin's anti-inflammatory properties, further studies are necessary to elucidate its complex regulatory mechanisms in different cellular types and tissues.

This paper is a catalogue of all syntaxa from class to association ever described and recognized in Spain and Portugal (Iberian Peninsula, Balearic, Madeira, Azorean and Canary Islands), according with Braun-Blanquet approach (Braun-Blanquet 1964, Dierschke 1994) and the International Code of Phytosociological Nomenclature (Weber, Moravec & Theurillat 2000). The literature contents near all the publications cited in this paper, particularly those of portuguese and spanish syntaxa authors. The Syntaxonomical Checklist of Spain and Portugal, prepared during the last ten years as a bassis of the Luso-Hispaniae Prodromus of the Plant Communities (in progress), has been reciprocally utilized to carry out the Syntaxonomical Project of European Community Countries (Biondi, Gehu, Grabherr, Pott & Rivas-Martinez, in progress), to assist the European Vegetation Survey (Rodwell, Mucina, Pignatti, Schaminee & Chytrý 1997), and to develop the phytosociological knowledge in the interpretation and evaluation of European Habitat Directive for conservation and management purposes

The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their "retrotype" and morphological traits dispersed across Eurasia and Africa via separate migratory episodes. Relicts of the first migrations include the Mouflon, as well as breeds previously recognized as "primitive" on the basis of their morphology, such as the Orkney, Soay, and the Nordic short-tailed sheep now confined to the periphery of northwest Europe. A later migratory episode, involving sheep with improved production traits, shaped the great majority of present-day breeds. The ability to differentiate genetically primitive sheep from more modern breeds provides valuable insights into the history of sheep domestication.

TR4 is of great concern due to the limited knowledge about key aspects of disease epidemiology and the lack of effective management models, including resistant varieties and soil management approaches. In this review we summarize the current knowledge on the epidemiology of FW of banana, highlighting knowledge gaps in pathogen survival and dispersal, factors driving disease intensity, soil and plant microbiome and the dynamics of the disease. Comparisons with FW in other crops were also made to indicate possible differences and commonalities. Our current understanding of the role of main biotic and abiotic factors on disease intensity is reviewed, highlighting research needs and futures directions. Finally, a set of practices and their impact on disease intensity are discussed and proposed as an integrative management approach that could eventually be used by a range of users, including plant protection organizations, researchers, extension workers and growers.

Endoplasmic reticulum (ER) is a dynamic organelle that participates in a number of cellular functions by controlling lipid metabolism, calcium stores, and proteostasis. Under stressful situations, the ER environment is compromised, and protein maturation is impaired; this causes misfolded proteins to accumulate and a characteristic stress response named unfolded protein response (UPR). UPR protects cells from stress and contributes to cellular homeostasis re-establishment; however, during prolonged ER stress, UPR activation promotes cell death. ER stressors can modulate autophagy which in turn, depending of the situation, induces cell survival or death. Interactions of different autophagy- and apoptosis-related proteins and also common signaling pathways have been found, suggesting an interplay between these cellular processes, although their dynamic features are still unknown. A number of pathologies including metabolic, neurodegenerative and cardiovascular diseases, cancer, inflammation, and viral infections are associated with ER stress, leading to a growing interest in targeting components of the UPR as a therapeutic strategy. Melatonin has a variety of antioxidant, anti-inflammatory, and antitumor effects. As such, it modulates apoptosis and autophagy in cancer cells, neurodegeneration and the development of liver diseases as well as other pathologies. Here, we review the effects of melatonin on the main ER stress mechanisms, focusing on its ability to regulate the autophagic and apoptotic processes. As the number of studies that have analyzed ER stress modulation by this indole remains limited, further research is necessary for a better understanding of the crosstalk between ER stress, autophagy, and apoptosis and to clearly delineate the mechanisms by which melatonin modulates these responses.

In this paper, we explore the evolution of consumers' perceptions and concerns about the effects that intensification of production systems could have on the welfare of farm animals. Despite the differences in definitions of animal welfare that make perceptions about this complex subject extremely variable, there is a growing perception that farm animal welfare should be protected and improved. There is an increasing appreciation of animal welfare parameters over other quality attributes, and animal-friendly products are considered healthier, safer, tastier, more hygienic, authentic, environmentally friendly, and traditional by many consumers. The willingness to pay for the increases in price that higher levels of farm animal welfare could produce could be promoted by means of adequate information about management and housing conditions of the different farming species. Welfare-friendly products that are properly labeled with clear information provided by an internationally accepted, transparent, and traceable monitoring system will increase consumers' confidence in the food chain participants. Both consumers and citizens have the opportunity to improve the welfare of millions of farmed animals now and in the future, consumers by assuming their responsibility at the buying point, purchasing welfare-friendly products, and citizens by driving legislation to achieve some minimum standard of welfare conditions that could meet animals' needs.

Telecollaboration, or ‘virtual exchange’, are terms used to refer to the engagement of groups of learners in online intercultural interactions and collaboration projects with partners from other cultural contexts or geographical locations as an integrated part of their educational programmes. In recent years, approaches to virtual exchange have evolved in different contexts and different areas of education, and these approaches have had, at times, very diverse organisational structures and pedagogical objectives. This article provides an overview of the different models and approaches to virtual exchange which are currently being used in higher education contexts. It also provides a short historical review of the major developments and trends in virtual exchange to date and describes the origins of the UNICollaboration organisation and the rationale behind this journal.

Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.

Experience economy is the last segment in the evolution of the market, and it is characterized by the fact that consumers do not acquire goods, products or services, but experiences that they integrate in their biography, and consequently in their identity. Customer Experience, possibly the latest revolution in business thinking along with the digital transformation, seeks the design and management of truly customer-centric experiences. This revolution is spreading across different sectors, among which the health sector should necessarily be considered. This talk covers the fundamental ideas within the concept of customer experience, as well as it provides information and suggestions about how to design and deliver an optimal patient experience.

Societal Impact Statement There is increasing awareness that plants and fungi, as natural solutions, can play an important role in tackling ongoing global environmental challenges. We illustrate how understanding current and projected threats to plants and fungi is necessary to manage and mitigate risks, while building awareness of gaps and bias in current assessment coverage is essential to adequately prioritize conservation efforts. We highlight the state of the art in conservation science and point to current methods of assessment and future studies needed to mitigate species extinction. Summary Plant and fungal biodiversity underpin life on earth and merit careful stewardship in an increasingly uncertain environment. However, gaps and biases in documented extinction risks to plant and fungal species impede effective management. Formal extinction risk assessments help avoid extinctions, through engagement, financial, or legal mechanisms, but most plant and fungal species lack assessments. Available global assessments cover c. 30% of plant species (ThreatSearch). Red List coverage overrepresents woody perennials and useful plants, but underrepresents single‐country endemics. Fungal assessments overrepresent well‐known species and are too few to infer global status or trends. Proportions of assessed vascular plant species considered threatened vary between global assessment datasets: 37% (ThreatSearch), and 44% (International Union for Conservation of Nature Red List of Threatened Species). Our predictions, correcting for several quantifiable biases, suggest that 39% of all vascular plant species are threatened with extinction. However, other biases remain unquantified, and may affect our estimate. Preliminary trend data show plants moving toward extinction. Quantitative estimates based on plant extinction risk assessments may understate likely biodiversity loss: they do not fully capture the impacts of climate change, slow‐acting threats, or clustering of extinction risk, which could amplify loss of evolutionary potential. The importance of extinction risk estimation to support existing and emerging conservation initiatives is likely to grow as threats to biodiversity intensify. This necessitates urgent and strategic expansion of efforts toward comprehensive and ongoing assessment of plant and fungal extinction risk.

OBJECTIVE The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention. RESEARCH DESIGN AND METHODS Overweight/obese adults with metabolic syndrome aged 55–75 years (n = 626) were randomized to an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively. RESULTS Diet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG (P &amp;lt; 0.001), a mean difference of −2.5 kg (95% CI −3.1 to −1.9). Weight loss ≥5% occurred in 33.7% of IG participants compared with 11.9% in the CG (P &amp;lt; 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL cholesterol, significantly improved in IG participants (P &amp;lt; 0.002). Reductions in insulin resistance, HbA1c, and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants (P &amp;lt; 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL cholesterol levels compared with their CG counterparts. CONCLUSIONS PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes.

BACKGROUND: Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases. OBJECTIVE: To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection. PATIENTS: 34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL). METHODS: Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index. RESULTS: Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively). CONCLUSIONS: Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 with fatty liver. Translocation of this fatty acid transporter to the plasma membrane of hepatocytes may contribute to liver fat accumulation in patients with NAFLD and HCV.