Formation of virus-like clusters is an intrinsic property of the tumor necrosis factor family member BAFF (B cell activating factor).

The oligomeric state of BAFF (B cell activing factor), a tumor necrosis factor (TNF) family cytokine that plays a critical role in B cell development and survival, has been the subject of recent debate. Myc-tagged BAFF starting at residue Gln136 was previously reported to crystallize as trimers at pH 4.5, whereas a histidine-tagged construct of BAFF, starting at residue Ala134, formed a virus-like cluster containing 60 monomers when crystallized at pH 9.0. The formation of the BAFF 60-mer was pH dependent, requiring pH >or= 7.0. More recently, 60-mer formation was suggested to be artificially induced by the histidine tag, and it was proposed that BAFF, like all other TNF family members, is trimeric. We report here that a construct of BAFF with no amino-terminal tag (Ala134-BAFF) can form a 60-mer in solution. Using size exclusion chromatography and static light scattering to monitor trimer to 60-mer ratios in BAFF preparations, we find that 60-mer formation is pH-dependent and requires histidine 218 within the DE loop of BAFF. Biacore measurements established that the affinity of Ala134-BAFF for the BAFF receptor BAFFR/BR3 is similar to that of myc-Gln136-BAFF, which is exclusively trimeric in solution. However, Ala134-BAFF is more efficacious than myc-Gln136-BAFF in inducing B cell proliferation in vitro. We additionally show that BAFF that is processed and secreted by 293T cells transfected with full-length BAFF, or by a histiocytic lymphoma cell line (U937) that expresses BAFF endogenously, forms a pH-dependent 60-mer in solution. Our results indicate that the formation of the 60-mer in solution by the BAFF extracellular domain is an intrinsic property of the protein, and therefore that this more active form of BAFF may be physiologically relevant.

Auditory localisation and recognition after left inferior collicular lesion: effects of work load on cortical activation patterns (fMRI study)

Evidence from neuropsychological and activation studies (Clarke et al., 2oo0, Maeder et al., 2000) suggests that sound recognitionand localisation are processed by two anatomically and functionally distinct cortical networks. We report here on a case of a patientthat had an interruption of auditory information and we show: i) the effects of this interruption on cortical auditory processing; ii)the effect of the workload on activation pattern.A 36 year old man suffered from a small left mesencephalic haemotrhage, due to cavernous angioma; the let% inferior colliculuswas resected in the surgical approach of the vascular malformation. In the acute stage, the patient complained of auditoryhallucinations and of auditory loss in right ear, while tonal audiometry was normal. At 12 months, auditory recognition, auditorylocalisation (assessed by lTD and IID cues) and auditory motion perception were normal (Clarke et al., 2000), while verbal dichoticlistening was deficient on the right side.Sound recognition and sound localisation activation patterns were investigated with fMRI, using a passive and an activeparadigm. In normal subjects, distinct cortical networks were involved in sound recognition and localisation, both in passive andactive paradigm (Maeder et al., 2OOOa, 2000b).Passive listening of environmental and spatial stimuli as compared to rest strongly activated right auditory cortex, but failed toactivate left primary auditory cortex. The specialised networks for sound recognition and localisation could not be visual&d onthe right and only minimally on the left convexity. A very different activation pattern was obtained in the active condition wherea motor response was required. Workload not only increased the activation of the right auditory cortex, but also allowed theactivation of the left primary auditory cortex. The specialised networks for sound recognition and localisation were almostcompletely present in both hemispheres.These results show that increasing the workload can i) help to recruit cortical region in the auditory deafferented hemisphere;and ii) lead to processing auditory information within specific cortical networks.References:Clarke et al. (2000). Neuropsychologia 38: 797-807.Mae.der et al. (2OOOa), Neuroimage 11: S52.Maeder et al. (2OOOb), Neuroimage 11: S33

Aportaciones al proceso de iberización en el curso inferior del Ebro: el ejemplo de Sebes (Flix, Ribera d’Ebre, Tarragona)

Presentamos en este trabajo el resultado de las intervenciones efectuadas en el yacimiento de Sebes entre los años 2010 y 2011, donde hemos podido documentar la existencia de un asentamiento ibérico de nueva planta fechado en la segunda mitad del siglo vi a.C., poco tiempo después del abandono del asentamiento del Hierro I, ubicado en la parte más alta de la colina de Sebes. La proximidad entre los dos asentamientos y los restos materiales recuperados parecen indicar un ligero traslado poblacional, dentro de una dinámica interna de cambio en la sociedad ibérica, en una etapa de transición previa a la consolidación de un nuevo modelo poblacional durante el siglo v a.C.

The Oncogene Metadherin Modulates the Apoptotic Pathway Based on the Tumor Necrosis Factor Superfamily Member TRAIL (Tumor Necrosis Factor-related Apoptosis-inducing Ligand) in Breast Cancer.

Metadherin (MTDH), the newly discovered gene, is overexpressed in more than 40% of breast cancers. Recent studies have revealed that MTDH favors an oncogenic course and chemoresistance. With a number of breast cancer cell lines and breast tumor samples, we found that the relative expression of MTDH correlated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in breast cancer. In this study, we found that knockdown of endogenous MTDH cells sensitized the MDA-MB-231 cells to TRAIL-induced apoptosis both in vitro and in vivo. Conversely, stable overexpression of MTDH in MCF-7 cells enhanced cell survival with TRAIL treatment. Mechanically, MTDH down-regulated caspase-8, decreased caspase-8 recruitment into the TRAIL death-inducing signaling complex, decreased caspase-3 and poly(ADP-ribose) polymerase-2 processing, increased Bcl-2 expression, and stimulated TRAIL-induced Akt phosphorylation, without altering death receptor status. In MDA-MB-231 breast cancer cells, sensitization to TRAIL upon MTDH down-regulation was inhibited by the caspase inhibitor Z-VAD-fmk (benzyloxycarbonyl-VAD-fluoromethyl ketone), suggesting that MTDH depletion stimulates activation of caspases. In MCF-7 breast cancer cells, resistance to TRAIL upon MTDH overexpression was abrogated by depletion of Bcl-2, suggesting that MTDH-induced Bcl-2 expression contributes to TRAIL resistance. We further confirmed that MTDH may control Bcl-2 expression partly by suppressing miR-16. Collectively, our results point to a protective function of MTDH against TRAIL-induced death, whereby it inhibits the intrinsic apoptosis pathway through miR-16-mediated Bcl-2 up-regulation and the extrinsic apoptosis pathway through caspase-8 down-regulation.

Carbon-isotope stratigraphy of the Liesberg Beds Member (Oxfordian, Swiss Jura) using echinoids and crinoids

The Liesberg Beds form the transition between the lower Oxfordian dark coloured marls (Renggeri Member and the Terrain a Chailles Member) and the middle Oxfordian reefal limestones (St-Ursanne Formation). Both lithofacies and biofacies are diverse and evolve rapidly up-section. Stable isotope studies of whole-rock samples are therefore excluded. In search for a convenient isotopic marker, we measured carbon isotope compositions of several fossil groups and chose crinoid stems of Millericrinus spp and echinoid spines of Paracidaris spp because of their abundance throughout the section and the small variations of delta(13)C within one fossil and between fossils from the same stratigraphic level. The delta(13)C values of echinoderms largely reflect earliest diagenetic conditions at the seawatersediment interface. The porous stereome structure secreted of high Mg-calcite by echinoderms has a high reactive surface/volume ratio, which triggers the precipitation of very early syntaxial cements. In the four studied sections reproducible carbon isotope shifts were observed both for Millericrinus spp stems and Paracidaris spp spines. A negative delta(13)C shift of 1-1.5 parts per thousand was observed near the base of the section, just above the transition from Terrain a Chailles Member, where the first corals occur. In the middle and upper part of the four sections, characterised by a stepwise increase of corals and the macrofossils, a positive delta(13)C Shift of about 2 parts per thousand was observed. Despite the highly variable lithologic composition of the Liesberg Beds;Member, carbon isotope shifts seem to be consistent and warrant an interpretation as an original signal, controlled by the isotopic composition of dissolved carbonic acid in seawater. We explain the heavy delta(13)C values (approximate to 2-2.3 parts per thousand) in the lower Liesberg Beds as a transition from an oxygen-limited environment (Terrain a Chailles Member) to the Liesberg Beds Member. The lowest delta(13)C values (approximate to 1-1.5 parts per thousand) correspond to a large input of dissolved nutrients to the platform under oxidizing conditions. The ensuing positive shift (between 2.5 and 3.5 parts per thousand), however, seems to correspond to a general trend of opening up of the platform and connection to open marine waters. Positive delta(13)C values in the upper Liesberg Beds is interpreted as a result of important accelareted extraction of organic carbon from the ocean reservoir, that occurred possibly during periods of warm and humid climate.

Anterior inferior cerebellar artery aneurysms mimicking vestibular schwannomas.

BACKGROUND AND PURPOSE: Unruptured anterior inferior cerebellar artery (AICA) aneurysms are rare but potentially lethal cerebellopontine angle (CPA) lesions that may be misdiagnosed as vestibular schwannomas when they present with vestibulo-cochlear symptoms. METHODS: We report two cases of unruptured but symptomatic AICA aneurysms initially referred to us as atypical vestibular schwannomas requiring surgery. Two discriminant MR features are described. RESULTS: One patient refused treatment. The other was successfully treated by coil occlusion. CONCLUSIONS: Caution is advised before suspecting a CPA mass to be a purely extra-canalicular schwannoma, given its extreme rarity. Deafness and cerebellar ischemia may be prevented if AICA aneurysms are correctly identified preoperatively. In the absence of specific arterial imaging, two MR features may distinguish them from vestibular schwannomas: (1) the absence of internal auditory canal enlargement and (2) the "blurry dot sign," representing blood flow artefacts on pre- and postcontrast studies.

Los inicios de la conquista romana de Iberia: los campamentos de campaña del curso inferior del río Ebro

La investigación arqueológica de los campamentos de campaña romano-republicanos localizados en el curso inferior del río Ebro permite una nueva perspectiva de estudio sobre los inicios de la conquista romana en la península ibérica.

European Union Eastern Enlargement - Expectations and Experiences of Doing Business in the New Member States

This publication deals with various aspects of European Union enlargement effects faced by the companies from EU15 and especially from Finland when doing business in the ten transitional economies which joined European Union in 2004 and 2007

Espigueo por la toponimia mayor del Valle Medio e Inferior del Ésera (Huesca)

El present treball pretén donar llum a una sèrie de topònims majors de la Ribagorça occidental, tot al llarg de la vall mitjana i inferior del riu Éssera. Aquests topònims es remunten a temps molt antics: preromans, romans i germànics bàsicament. Aquesta anàlisi permet apreciar l'estratigrafi a lingüística de la zona. La no-aparició de topònims d'origen àrab en el nostre treball no vol dir que no hi hagués penetració àrab a la zona, sinó que la seva arribada va ser posterior a la creació dels principals nuclis de població. Sí que hi ha topònims àrabs a la toponímia menor, que resta fora del present treball.

The AMPK family member Snf1 protects Saccharomyces cerevisiae cells upon glutatione oxidation

The AMPK/Snf1 kinase has a central role in carbon metabolism homeostasis in Saccharomyces cerevisiae. In this study, we show that Snf1 activity, which requires phosphorylation of the Thr210 residue, is needed for protection against selenite toxicity. Such protection involves the Elm1 kinase, which acts upstream of Snf1 to activate it. Basal Snf1 activity is sufficient for the defense against selenite, although Snf1 Thr210 phosphorylation levels become increased at advanced treatment times, probably by inhibition of the Snf1 dephosphorylation function of the Reg1 phosphatase. Contrary to glucose deprivation, Snf1 remains cytosolic during selenite treatment, and the protective function of the kinase does not require its known nuclear effectors. Upon selenite treatment, a null snf1 mutant displays higher levels of oxidized versus reduced glutathione compared to wild type cells, and its hypersensitivity to the agent is rescued by overexpression of the glutathione reductase gene GLR1. In the presence of agents such as diethyl maleate or diamide, which cause alterations in glutathione redox homeostasis by increasing the levels of oxidized glutathione, yeast cells also require Snf1 in an Elm1-dependent manner for growth. These observations demonstrate a role of Snf1 to protect yeast cells in situations where glutathione-dependent redox homeostasis is altered to a more oxidant intracellular environment and associates AMPK to responses against oxidative stress.

Léiomyosarcome de la veine cave inférieure. A propos de trois observations [Leiomyosarcoma of the inferior vena cava. Three cases].

We report three new cases of leiomyosarcoma of the inferior vena cava observed between 1985 and 1990. Two of them developed in women and one in a man. The age of the patients were 56, 29 and 57 years. The three tumors have been removed completely. One patient received postoperative radio- and chemotherapy and is well 68 months after excision. One patient developed liver metastasis 18 months after resection despite chemotherapy and died after 3 years. The last one refused postoperative radio- and chemotherapy, developed massive local recurrence and pulmonary metastasis three months postoperatively, and is still alive with disease after 8 months. The diagnostic modalities of these rare tumors as well as the problems created by their surgical resection and the need for a complementary treatment are discussed.

Unidades fototérmicas e temperatura-base inferior de frutos de Mangueira Alfa, na Baixada Cuiabana

O objetivo deste trabalho foi determinar a temperatura-base inferior (Tb) a partir da unidade fototérmica (UF) para o cultivo experimental de manga Alfa sob condições de cerrado. Foram utilizados dados diários da temperatura do ar disponibilizados pela Estação Agrometeorológica Padre Ricardo Remetter, localizada em Santo Antônio do Leverger-MT (15,8° S e 56,1° W, 140 m), e avaliação sensorial do estádio de maturação dos frutos de manga. A Tb foi determinada pelo método da menor variabilidade das unidades fototérmicas (UF) acumuladas do período da floração à colheita dos frutos, variabilidade avaliada pelo coeficiente de variação (cv) simulado para diferentes valores da Tb. De julho a novembro de 2007, em três plantas de um pomar demonstrativo irrigado, foram identificados 82 frutos para o acompanhamento do crescimento e maturação. Entre esses frutos, em meados de dezembro de 2007, foi possível identificar 13 frutos que atingiram a maturidade fisiológica, após um período médio de observação de 112 dias. Para exigência fototérmica de 1.878.166,1 UF, encontrou-se Tb de 10 °C, valor consistente com os apresentados na literatura para a cultivar de manga, o que comprova a eficiência do método que combina a ação da temperatura e do fotoperíodo sobre a maturação dos frutos e que confere um caráter mais racional que o método tradicional da soma térmica.