tRNA-derived fragments target the small ribosomal subunit to fine-tune translation

Post-transcriptional cleavage of RNA molecules to generate smaller fragments is a widespread mechanism that enlarges the structural and functional complexity of cellular RNomes. In particular, fragments deriving from both precursor and mature tRNAs represent one of the rapidly growing classes of post-transcriptional RNA pieces. Importantly, these tRNA-derived fragments (tRFs) possess distinct expression patterns, abundance, cellular localizations, or biological roles compared with their parental tRNA molecules (1). Here we present evidence that tRFs from the archaeon Haloferax volcanii directly bind to ribosomes. In a previous genomic screen for ribosome-associated small RNAs we have identified a 26 residue long fragment originating from the 5’ part of valine tRNA (Val-tRF) to be by far the most abundant tRF in H. volcanii (2). The Val-tRF is processed in a stress- dependent manner and was found to primarily target the small ribosomal subunit in vitro and in vivo. Translational activity was markedly reduced in the presence of Val-tRF, while control RNA fragments of similar length did not show inhibition of protein biosynthesis. Crosslinking experiments and subsequent primer extension analyses revealed the Val-tRF interaction site to surround the mRNA path in the 30S subunit. In support of this, binding experiments demonstrated that Val-tRF does compete with mRNAs for ribosome binding. Therefore this tRF represents a ribosome-bound non-protein-coding RNA (ncRNA) capable of regulating gene expression in H. volcanii under environmental stress conditions probably by fine-tuning the rate of protein production (1). (1) Gebetsberger J. and Polacek N. (2013), RNA Biol. 10:1798-1808 (2) Gebetsberger J. et. al. (2012), Archaea, Article ID 260909

Strange Relations. Cultural Translation of Noh Theatre in Ezra Pound’s Dance Poems and W. B. Yeats’s At the Hawk’s Well

Drawing on the reception of Noh drama by Ezra Pound and William Butler Yeats, the article analyses both the literary and cultural ‘translations’ of this form of Japanese theatre in their works, focusing on Yeats’s play At the Hawk’s Well (1917). I conceptualize ‘cultural translation’ as the staging of relations that mark a residual cultural difference. Referred to as ‘foreignizing’ in translation theory, this method enables what Erika Fischer-Lichte has termed a ‘liminal experience’ for the audience –– an effect Yeats intended for the performance of his play. It evokes situations in which opposites collapse and new ways of acting or new combinations of symbols can be tried out. Yeats’s play will be used to sketch how an analysis of relations could serve as a general model for the study of cultural transfer as cultural translation in general. Keywords: cultural translation, translation theory, performance, William Butler Yeats, Itō Michio, Ezra Pound, At the Hawk’s Well

ACL reconstruction with physiological graft tension by intraoperative adjustment of the anteroposterior translation to the uninjured contralateral knee.

PURPOSE Fixation of anterior cruciate ligament (ACL) substitutes with non-physiological anteroposterior translation (APT) worsens outcome. The aim was to present a technique for physiological APT adjustment of the transplant in ACL reconstruction and its outcome at midterm. METHODS In a consecutive series of 28 patients (age 32 ± 11 years, 24 male), chronic ACL deficiency was treated by bone-patella-tendon-bone reconstruction. Transplant APT was adjusted to that of the contralateral uninjured ACL, measured 3, 6, and 12 months postoperatively using the Rolimeter. At a median follow-up of 5.3 years (3-8 years), 82% of the patients were re-evaluated with APT measurement and using IKDC-, Tegner-, Lysholm-Scores, conventional radiographs and MRI. RESULTS No differences in APT (mean ± SD) between uninjured and reconstructed knees were observed after adjustment (6 ± 1 versus 6 ± 1 mm, n.s.). Three months postoperatively, a statistically significant increase in APT (7 ± 1 mm) and a further increase at midterm (9 ± 2 mm) were observed. Patients scored "normal" or "nearly normal", respectively, in 79% (IKDC) and 4 (3-9) points (Tegner; median, range) or 89 ± 9 points (Lysholm; mean ± SD). Radiological evaluation showed no, minimal or moderate joint degeneration in 5, 20 and 75% of patients, respectively. MRI confirmed intact ACL transplants in all patients. CONCLUSION ACL reconstruction using the presented technique was considered successful, as patients did not suffer from subjective instability, radiographic analysis did not provide evidence for graft rupture at midterm. However, APT increase and occurrence of degenerative changes in reconstructed knees at the midterm might not be prevented even by restoration of a physiological APT in ACL reconstruction. The Rolimeter can be used for quick and easy intraoperative indirect control of the applied tension to the ACL transplant by measuring the APT to obtain physiological tensioning resulting in a satisfying outcome at midterm. LEVEL OF EVIDENCE IV.

Ribosome-associated ncRNAs: An emerging class of translation regulators

Accumulating recent evidence identified the ribosome as binding target for numerous small and long non-protein-coding RNAs (ncRNAs) in various organisms of all 3 domains of life. Therefore it appears that ribosome-associated ncRNAs (rancRNAs) are a prevalent, yet poorly understood class of cellular transcripts. Since rancRNAs are associated with the arguable most central enzyme of the cell it seems plausible to propose a role in translation control. Indeed first experimental evidence on small rancRNAs has been presented, linking ribosome association with fine-tuning the rate of protein biosynthesis in a stress-dependent manner.

Hippocampus is place of interaction between unconscious and conscious memories retrieval

Recent experiments suggest that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus - the key structure thought to support conscious relational (episodic) memory. Given that the hippocampus subserves both conscious and unconscious relational encoding/retrieval, we expected the hippocampus to be place of unconscious-conscious interactions. This hypothesis was tested in an fMRI experiment on the interaction between the unconscious retrieval of face-associated occupations and the subsequent conscious retrieval of celebrities’ occupations. For subliminal encoding, masked combinations of an unfamiliar face and a written occupation (“actor” or “politician”) were subliminally presented. At test, we presented the former subliminal faces again, without occupations and masks, as conscious retrieval cues. We hypothesized that faces would trigger the unconscious reactivation of the associated occupation - actor or politician -, which in turn would facilitate or inhibit the subsequent conscious recollection of a celebrity’s occupation. Following the presentation of a former subliminal face, we presented the portrait of a celebrity that participants were required to sort according to “actor” or “politician”. Depending on whether the triggered unconscious occupation was congruent or incongruent with the celebrity’s occupation, we expected an expedited or retarded conscious retrieval process as reflected in reaction times. Conscious retrieval was expedited in the congruent condition, but there was no effect in the incongruent condition. fMRI data collected during subliminal relational encoding confirmed that the hippocampus was interacting with neocortical semantic storage sites. fMRI data collected at test indicated that the facilitated conscious retrieval of celebrity-associated occupations was related to deactivations in this same network spanning hippocampus and neocortical semantic storage sites. Hence, unconscious retrieval likely preactivated this network, which allowed for a sparing recruitment of additional neural resources to assist conscious retrieval. This finding supports the notion that consciously and unconsciously acquired relational memories are stored in a single, cohesive hippocampal-neocortical memory space.

Self-replicating Replicon-RNA Delivery to Dendritic Cells by Chitosan-nanoparticles for Translation In Vitro and In Vivo.

Self-amplifying replicon RNA (RepRNA) possesses high potential for increasing antigen load within dendritic cells (DCs). The major aim of the present work was to define how RepRNA delivered by biodegradable, chitosan-based nanoparticulate delivery vehicles (nanogel-alginate (NGA)) interacts with DCs, and whether this could lead to translation of the RepRNA in the DCs. Although studies employed virus replicon particles (VRPs), there are no reports on biodegradable, nanoparticulate vehicle delivery of RepRNA. VRP studies employed cytopathogenic agents, contrary to DC requirements-slow processing and antigen retention. We employed noncytopathogenic RepRNA with NGA, demonstrating for the first time the efficiency of RepRNA association with nanoparticles, NGA delivery to DCs, and RepRNA internalization by DCs. RepRNA accumulated in vesicular structures, with patterns typifying cytosolic release. This promoted RepRNA translation, in vitro and in vivo. Delivery and translation were RepRNA concentration-dependent, occurring in a kinetic manner. Including cationic lipids with chitosan during nanoparticle formation enhanced delivery and translation kinetics, but was not required for translation of immunogenic levels in vivo. This work describes for the first time the characteristics associated with chitosan-nanoparticle delivery of self-amplifying RepRNA to DCs, leading to translation of encoded foreign genes, namely influenza virus hemagglutinin and nucleoprotein.

Hippocampus Is Place of Interaction between Unconscious and Conscious Memories.

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations ("actor" or "politician"). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space.