Search results for "Translational"
showing 10 items of 418 documents
Fertility and Polarized Cell Growth Depends on eIF5A for Translation of Polyproline-Rich Formins in Saccharomyces cerevisiae
2014
eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a proline-rich formin involved in polarized growth during …
Interleukin-7 matures suppressive CD127(+) forkhead box P3 (FoxP3)(+) T cells into CD127(-) CD25(high) FoxP3(+) regulatory T cells.
2011
We have identified a novel interleukin (IL)-7-responsive T cell population [forkhead box P3 (FoxP3(+) ) CD4(+) CD25(+) CD127(+) ] that is comparably functionally suppressive to conventional FoxP3(+) CD4(+) CD25(+) regulatory T cells (T(regs) ). Although IL-2 is the most critical cytokine for thymic development of FoxP3(+) T(regs) , in the periphery other cytokines can be compensatory. CD25(+) CD127(+) T cells treated with IL-7 phenotypically 'matured' into the known 'classical' FoxP3(+) CD4(+) CD25(high) CD127(-) FoxP3(+) T(regs) . In freshly isolated splenocytes, the highest level of FoxP3 expression was found in CD127(+) CD25(+) T cells when compared with CD127(-) CD25(+) or CD127(+) CD25…
In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients.
2010
The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T …
Translational diffusion coefficients of volatile compounds in various aqueous solutions at low and subzero temperatures.
2005
International audience; Translational diffusion coefficients (D(12)) of volatile compounds were measured in model media with the profile concentration method. The influence of sample temperature (from 25 to -10 degrees C) was studied on translational diffusion in sucrose or maltodextrin solutions at various concentrations. Results show that diffusivity of volatile compounds in sucrose solutions is controlled by temperature, molecule size, and the viscosity of the liquid phase as expected with the Stokes-Einstein equation; moreover, physicochemical interactions between volatile compounds and the medium are determinant for diffusion estimation. At negative temperature, the winding path induce…
A Trans-amplifying RNA Vaccine Strategy for Induction of Potent Protective Immunity
2019
Here, we present a potent RNA vaccine approach based on a novel bipartite vector system using trans-amplifying RNA (taRNA). The vector cassette encoding the vaccine antigen originates from an alphaviral self-amplifying RNA (saRNA), from which the replicase was deleted to form a transreplicon. Replicase activity is provided in trans by a second molecule, either by a standard saRNA or an optimized non-replicating mRNA (nrRNA). The latter delivered 10- to 100-fold higher transreplicon expression than the former. Moreover, expression driven by the nrRNA-encoded replicase in the taRNA system was as efficient as in a conventional monopartite saRNA system. We show that the superiority of nrRNA- ov…
Contribution of polyadenylate sequences to the translational efficiency of globin messenger RNAs
1987
mRNAs from reticulocyte polysomes were fractionated by chromatography on poly(U)-Sepharose and thermal elution. The molar ratio of alpha- to beta-globin mRNA was found to be 2:1 and 1:1 respectively in short- and long-poly(A) size classes. Translational analyses indicated that the globin mRNAs containing long poly(A) tracts (with a mean length of about 70 nucleotides) directed protein synthesis with higher rates than did mRNA containing short poly(A) tracts (15-35 nucleotides). Experiments performed with sub-saturating mRNA concentrations showed that the digestion with RNAase H induced a decrease in the translational capacity of both globin mRNAs and an increase in the alpha- to beta-globin…
Protease-mediated processing of Argonaute proteins controls small RNA association
2020
SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a cha…
From Bench to Bedside—The Bad Berka Experience With First-in-Human Studies
2019
Precision oncology is being driven by rapid advances in novel diagnostics and therapeutic interventions, with treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. Inherent in the theranostics paradigm is the assumption that diagnostic test results can precisely determine whether an individual is likely to benefit from a specific treatment. As part and integral in the current era of precision oncology, theranostics in the context of nuclear medicine aims to identify the appropriate molecular targets in neoplasms (diagnost…
Tributyltin(Iv) butyrate: A novel epigenetic modifier with er stress-and apoptosis-inducing properties in colon cancer cells
2021
Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric enviro…
NMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like domain from Tetrahymena thermophila polyubiquitin locus.
2019
Abstract Background Ubiquitin-like domains (UbLs), in addition to being post-translationally conjugated to the target through the E1-E2-E3 enzymatic cascade, can be translated as a part of the protein they ought to regulate. As integral UbLs coexist with the rest of the protein, their structural properties can differ from canonical ubiquitin, depending on the protein context and how they interact with it. In this work, we investigate T.th-ubl5, a UbL present in a polyubiquitin locus of Tetrahymena thermophila, which is integral to an ADP-ribosyl transferase protein. Only one other co-occurrence of these two domains within the same protein has been reported. Methods NMR, multiple sequence al…