Eukaryotic translation elongation factor 1A (eEF1A) domain I from S. cerevisiae is required but not sufficient for inter-species complementation

Ethanolamine phosphoglycerol (EPG) is a protein modification attached exclusively to eukaryotic elongation factor 1A (eEF1A). In mammals and plants, EPG is linked to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote Trypanosoma brucei, only domain III is modified by a single EPG. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but nothing is known about the EPG modifying enzyme(s). By expressing human eEF1A in T. brucei, we now show that EPG attachment to eEF1A is evolutionarily conserved between T. brucei and Homo sapiens. In contrast, S. cerevisiae eEF1A, which has been shown to lack EPG is not modified in T. brucei. Furthermore, we show that eEF1A cannot functionally complement across species when using T. brucei and S. cerevisiae as model organisms. However, functional complementation in yeast can be obtained using eEF1A chimera containing domains II or III from other species. In contrast, yeast domain I is strictly required for functional complementation in S. cerevisia

La philosophie religieuse des théoriciens bouddhistes de la connaissance

Programme de l’année 2006-2007 : Le programme et les arrière‑plans religieux de l’école logico‑épistémologique bouddhiqu

Thèmes philosophico-religieux dans la littérature gnomique et narrative bouddhique

Les conférences de l’année 2017-2018 se sont articulées autour de trois thèmes et modalités de l’interaction polémique entre élites bouddhiques et brahmaniques : démonstrations de la supériorité du Buddha sur les divinités du panthéon hindou/brahmanique ; critique de la violence rituelle ; vocation antibrahmanique de l’« avènement » du Buddha. En marge de leur critique, philosophique et solidement argumentée, des théologies brahmaniques d’un Dieu créateur (īśvara), les intellectuels bouddhist..

Aśvaghoṣa, poète du bouddhisme indien :sources, thèmes et arguments (II)

Durant l’année 2016-2017, nous avons poursuivi notre examen des œuvres d’Aśvaghoṣa, moine, poète et dramaturge bouddhiste du ier ou du iie siècle de notre ère. Tandis que la conférence de l’année précédente avait porté surtout sur l’affiliation « sectaire » d’Aśvaghoṣa, les légendes biographiques attachées à son nom et son historiographie (1830-1930 environ, soit jusqu’aux éditions de E. H. Johnston), celle de l’année 2016-2017 a été consacrée à deux thèmes corrélés, le saṃsāra ou « cycle de la transmigration/existence », et la royauté

Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA

Purpose: To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, 177Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. Methods: In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand 177Lu-AMBA was used and compared with established bombesin radioligands such as 125I-Tyr4-bombesin and 125I-[D-Tyr6,β-Ala11,Phe13,Nle14]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. Results: 177Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. 177Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with 177Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with 177Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with 177Lu-AMBA than with the conventional bombesin radioligands. Conclusion: The present in vitro study suggests that 177Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessel

TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis

[EN] We have identified in yeast a connection between two master regulators of cell growth: a biochemical connection involving the TORC1 protein kinase (which activates protein synthesis, nutrient uptake, and anabolism) and a biophysical connection involving the plasma membrane proton-pumping H+ -ATPase Pma1 (which drives nutrient and K+ uptake and regulates pH homeostasis). Raising the temperature to nonpermissive values in a TOR thermosensitive mutant decreases Pma1 activity. Rapamycin, a TORC1 inhibitor, inhibits Pma1 dependent on its receptor Fpr1 and on the protein phosphatase Sit4, a TORC1 effector. Mutation of either Sit4 or Tco89, a nonessential subunit of TORC1, decreases proton efflux, K+ uptake, intracellular pH, cell growth, and tolerance to weak organic acids. Tco89 does not affect Pma1 activity but activates K+ transport.We thank Prof. Michael N. Hall (Basel) for strains SH100 and SH221, and Prof. Joaquin Arino (Barcelona) for strain BY4741 and its null mutant derivatives fpr1 Delta 0, sit4 Delta 0, and tco89 Delta 0. We also thank Prof. Francisco Portillo (Madrid) for the antibody against the double phosphorylation of Ser911 Thr912 in Pma1. This work was funded by grant PROME-TEOII/2014/041 from Generalitat Valenciana (Valencia, Spain).Mahmoud, S.; Planes Ferrer, MD.; Cabedo López, M.; Trujillo, C.; Rienzo, A.; Caballero Molada, M.; Sharma, SC.... (2017). TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis. FEBS Letters. 591(13):1993-2002. https://doi.org/10.1002/1873-3468.12673S199320025911

Regulation of Translation by TOR, eIF4E and eIF2 alpha in Plants:Current Knowledge, Challenges and Future Perspectives

An important step in eukaryotic gene expression is the synthesis of proteins from mRNA, a process classically divided into three stages, initiation, elongation, and termination. Translation is a precisely regulated and conserved process in eukaryotes. The presence of plant-specific translation initiation factors and the lack of well-known translational regulatory pathways in this kingdom nonetheless indicate how a globally conserved process can diversify among organisms. The control of protein translation is a central aspect of plant development and adaptation to environmental stress, but the mechanisms are still poorly understood. Here we discuss current knowledge of the principal mechanisms that regulate translation initiation in plants, with special attention to the singularities of this eukaryotic kingdom. In addition, we highlight the major recent breakthroughs in the field and the main challenges to address in the coming years

Studies in Dhāraṇī Literature II: Pragmatics of Dhāraṇīs

This article is one of a series that reassesses the dhāraṇī texts of Mahāyāna Buddhism. The article seeks to examine dhāraṇī texts by using the linguistic tools of pragmatics, especially historical pragmatics, to assist the understanding of their statements. Rather than the meaning of the term dhāraṇī as a subject term, the domain of truth-conditional semantics, this paper examines statements in texts labelled dhāraṇī. Pragmatics examines meaning in context, and the categories of speech acts developed by Searle has been especially helpful in mapping out differences within such texts and the formalization of statements across texts. The grammaticalization of specific speech elements, especially interjections, in the context of mantra-dhāraṇīs is also discussed

The Lysosome and Intracellular Signalling.

In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed