Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut

Fish larval development, not least the spectacular process of flatfish metamorphosis, appears to be under complex endocrine control, many aspects of which are still not fully elucidated. In order to obtain data on the functional development of two major endocrine glands, the pituitary and the thyroid, during flatfish metamorphosis, histology, immunohistochemistry and in situ hybridization techniques were applied on larvae of the Atlantic halibut (Hippoglossus hippoglossus), a large, marine flatfish species, from hatching through metamorphosis. The material was obtained from a commercial hatchery. Larval age is defined as day-degrees (D =accumulated daily temperature from hatching). Sporadic thyroid follicles are first detected in larvae at 142 D (27 days post-hatch), prior to the completion of yolk sack absorption. Both the number and activity of the follicles increase markedly after yolk sack absorption and continue to do so during subsequent development. The larval triiodothyronine (T3) and thyroxine (T4) content increases, subsequent to yolk absorption, and coincides with the proliferation of thyroid follicles. A second increase of both T3 and T4 occurs around the start of metamorphosis and the T3 content further increases at the metamorphic climax. Overall, the T3 content is lower than T4. The pituitary gland can first be distinguished as a separate organ at the yolk sack stage. During subsequent development, the gland becomes more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia (PI). The first sporadic endocrine pituitary cells are observed at the yolk sack stage, somatotrophs (growth hormone producing cells) and somatolactotrophs (somatolactin producing cells) are first observed at 121 D (23 days post-hatch), and lactotrophs (prolactin producing cells) at 134 D (25 days post-hatch). Scarce thyrotrophs are evident after detection of the first thyroid follicles (142 D ), but coincident with a phase in which follicle number and activity increase (260 D ). The somatotrophs are clustered in the medium ventral region of the PD, lactotrophs in the anterior part of the PD and somatolactotrophs are scattered in the mid and posterior region of the pituitary. At around 600 D , coinciding with the start of metamorphosis, somatolactotrophs are restricted to the interdigitating tissue of the NH. During larval development, the pituitary endocrine cells become more numerous. The present data on thyroid development support the notion that thyroid hormones may play a significant role in Atlantic halibut metamorphosis. The time of appearance and the subsequent proliferation of pituitary somatotrophs, lactotrophs, somatolactotrophs and thyrotrophs indicate at which stages of larval development and metamorphosis these endocrine cells may start to play active regulatory roles.This work has been carried out within the projects ‘‘Endocrine Control as a Determinant of Larval Quality in Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The Molecular and Endocrine Basis of Flatfish Metamorphosis’’ (Q5RS-2002-01192), with financial support from the Commission of the European Communities. However, it does not necessarily reflect the Commission’s views and in no way anticipates its future policy in this area. This project was further supported by the Swedish Council for Agricultural and Forestry Research and Pluriannual funding to CCMAR by the Portuguese Science and Technology Council

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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Development of 100^{100}Mo-containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search

We report recent achievements in the development of scintillating bolometers to search for neutrinoless double-beta decay of $^{100}$Mo. The presented results have been obtained in the framework of the LUMINEU, LUCIFER and EDELWEISS collaborations, and are now part of the R\&D activities towards CUPID (CUORE Update with Particle IDentification), a proposed next-generation double-beta decay experiment based on the CUORE experience. We have developed a technology for the production of large mass ($\sim$1 kg), high optical quality, radiopure zinc and lithium molybdate crystal scintillators (ZnMoO$_4$ and Li$_2$MoO$_4$, respectively) from deeply purified natural and $^{100}$Mo-enriched molybdenum. The procedure is applied for a routine production of enriched crystals. Furthermore, the technology of a single detector module consisting of a large-volume ($\sim 100$~cm$^3$) Zn$^{100}$MoO$_4$ and Li$_2$$^{100}$MoO$_4$ scintillating bolometer has been established, demonstrating performance and radiopurity that are close to satisfy the demands of CUPID. In particular, the FWHM energy resolution of the detectors at 2615 keV --- near the $Q$-value of the double-beta transition of $^{100}$Mo (3034~keV) --- is $\approx$ 4--10~keV. The achieved rejection of $\alpha$-induced dominant background above 2.6~MeV is at the level of more than 99.9\%. The bulk activity of $^{232}$Th ($^{228}$Th) and $^{226}$Ra in the crystals is below 10 $\mu$Bq/kg. Both crystallization and detector technologies favor Li$_2$MoO$_4$, which was selected as a main element for the realization of a CUPID demonstrator (CUPID-0/Mo) with $\sim$7 kg of $^{100}$Mo

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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Search for dijet resonances in proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

Correction: DOI:10.1016/j.physletb.2017.09.029Peer reviewe

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

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Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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