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MicroRNAs regulate gene expression through deadenylation, repression, and messenger RNA (mRNA) decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild-type and dicer mutant zebrafish embryos and found that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation with use of an internal polyadenylate tail did not block target repression. Lastly, we observed that ribosome density along the length of the message remains constant, suggesting that translational repression occurs by reducing the rate of initiation rather than affecting elongation or causing ribosomal drop-off. These results show that miR-430 regulates translation initiation before inducing mRNA decay during zebrafish development.

The mechanism of ion channel voltage gating—how channels open and close in response to voltage changes—has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker—S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/caldum voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.

We used functional magnetic resonance imaging (fMRI) to longitudinally examine brain plasticity arising from long-term, intensive simultaneous interpretation training. Simultaneous interpretation is a bilingual task with heavy executive control demands. We compared brain responses observed during simultaneous interpretation with those observed during simultaneous speech repetition (shadowing) in a group of trainee simultaneous interpreters, at the beginning and at the end of their professional training program. Age, sex and language-proficiency matched controls were scanned at similar intervals. Using multivariate pattern classification, we found distributed patterns of changes in functional responses from the first to second scan that distinguished the interpreters from the controls. We also found reduced recruitment of the right caudate nucleus during simultaneous interpretation as a result of training. Such practice-related change is consistent with decreased demands on multilingual language control as the task becomes more automatized with practice. These results demonstrate the impact of simultaneous interpretation training on the brain functional response in a cerebral structure that is not specifically linguistic, but that is known to be involved in learning, in motor control, and in a variety of domain-general executive functions. Along with results of recent studies showing functional and structural adaptations in the caudate nuclei of experts in a broad range of domains, our results underline the importance of this structure as a central node in expertise-related networks. •Training in simultaneous interpretation reduces load on the right caudate nucleus.•Distributed patterns of functional change are revealed using multivariate methods.•Longitudinal results converge with cross-sectional ones in other domains of expertise.

Multicellular organs are composed of distinct cell types with unique assemblages of translated mRNAs. Here, ribosome-associated mRNAs were immunopurified from specific cell populations of intact seedlings using Arabidopsis thaliana lines expressing a FLAG-epitope tagged ribosomal protein L18 (FLAG-RPL18) via developmentally regulated promoters. The profiling of mRNAs in ribosome complexes, referred to as the translatome, identified differentially expressed mRNAs in 21 cell populations defined by cell-specific expression of FLAG-RPL18. Phloem companion cells of the root and shoot had the most distinctive translatomes. When seedlings were exposed to a brief period of hypoxia, a pronounced reprioritization of mRNA enrichment in the cell-specific translatomes occurred, including a ubiquitous rise in 49 mRNAs encoding transcription factors, signaling proteins, anaerobic metabolism enzymes, and uncharacterized proteins. Translatome profiling also exposed an intricate molecular signature of transcription factor (TF) family member mRNAs that was markedly reconfigured by hypoxia at global and cell-specific levels. In addition to the demonstration of the complexity and plasticity of cell-specific populations of ribosome-associated mRNAs, this study provides an in silico dataset for recognition of differentially expressed genes at the cell-, region-, and organ-specific levels.

The search for ever deeper relationships among the World’s languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some “ultraconserved” words exist that might be used to find evidence for deep linguistic relationships beyond that time barrier. Here we use a statistical model, which takes into account the frequency with which words are used in common everyday speech, to predict the existence of a set of such highly conserved words among seven language families of Eurasia postulated to form a linguistic superfamily that evolved from a common ancestor around 15,000 y ago. We derive a dated phylogenetic tree of this proposed superfamily with a time-depth of ∼14,450 y, implying that some frequently used words have been retained in related forms since the end of the last ice age. Words used more than once per 1,000 in everyday speech were 7- to 10-times more likely to show deep ancestry on this tree. Our results suggest a remarkable fidelity in the transmission of some words and give theoretical justification to the search for features of language that might be preserved across wide spans of time and geography.

Ribosome protection proteins (RPPs) confer tetracycline resistance by binding to the ribosome and chasing the drug from its binding site. The current model for the mechanism of action of RPPs proposes that drug release is indirect and achieved via conformational changes within the drug-binding site induced upon binding of the RPP to the ribosome. Here we report a cryo-EM structure of the RPP TetM in complex with the 70S ribosome at 7.2-Å resolution. The structure reveals the contacts of TetM with the ribosome, including interaction between the conserved and functionally critical C-terminal extension of TetM and the decoding center of the small subunit. Moreover, we observe direct interaction between domain IV of TetM and the tetracycline binding site and identify residues critical for conferring tetracycline resistance. A model is presented whereby TetM directly dislodges tetracycline to confer resistance.

For generations the study of vocal development and its role in language has been conducted laboriously, with human transcribers and analysts coding and taking measurements from small recorded samples. Our research illustrates a method to obtain measures of early speech development through automated analysis of massive quantities of day-long audio recordings collected naturalistically in children's homes. A primary goal is to provide insights into the development of infant control over infrastructural characteristics of speech through large-scale statistical analysis of strategically selected acoustic parameters. In pursuit of this goal we have discovered that the first automated approach we implemented is not only able to track children's development on acoustic parameters known to play key roles in speech, but also is able to differentiate vocalizations from typically developing children and children with autism or language delay. The method is totally automated, with no human intervention, allowing efficient sampling and analysis at unprecedented scales. The work shows the potential to fundamentally enhance research in vocal development and to add a fully objective measure to the battery used to detect speech-related disorders in early childhood. Thus, automated analysis should soon be able to contribute to screening and diagnosis procedures for early disorders, and more generally, the findings suggest fundamental methods for the study of language in natural environments.

Living cells maintain a steady state of biochemical reaction rates by exchanging energy and matter with the environment. These exchanges usually do not occur in in vitro systems, which consequently go to chemical equilibrium. This in turn has severely constrained the complexity of biological networks that can be implemented in vitro. We developed nanoliter-scale microfluidic reactors that exchange reagents at dilution rates matching those of dividing bacteria. In these reactors we achieved transcription and translation at steady state for 30 h and implemented diverse regulatory mechanisms on the transcriptional, translational, and posttranslational levels, including RNA polymerases, transcriptional repression, translational activation, and proteolysis. We constructed and implemented an in vitro genetic oscillator and mapped its phase diagram showing that steady-state conditions were necessary to produce oscillations. This reactor-based approach will allow testing of whether fundamental limits exist to in vitro network complexity.

This article investigates the temporal and aspectual composition of infinitival complementation structures in English. I show that previous classifications of tense in infinitives are insufficient in that they do not cover the entire spectrum of infinitival constructions in English. Using the distribution of nongeneric, nonstative, episodic interpretations as a main characteristic, I show that infinitival constructions fall into three classes: future irrealis infinitives, which allow episodic interpretations with bare VPs; simultaneous infinitives that do not allow episodic interpretations; and simultaneous infinitives that allow episodic interpretations depending on the matrix tense. I argue that the three classes of infinitives are derived from the following properties: future infinitives are tenseless but involve a syntactically present future modal woll; simultaneous propositional attitude infinitives impose the NOW of the propositional attitude holder as the reference time of the infinitive; and certain simultaneous infinitives form a single temporal domain with the matrix clause. The analysis proposed has consequences for the composition of tense and aspect, the syntax of infinitives, and the way selection is determined.

Simultaneous interpretation is a cognitively demanding process that requires a high level of language management. Previous studies on bilinguals have suggested that extensive practice managing two languages leads to enhancements in cognitive control. Thus, interpreters may be expected to show benefits beyond those seen in bilinguals, either as an extension of previously-seen benefits or in areas specific to interpretation. The present study examined professional interpreters (N = 23) and matched multilinguals (N = 21) on memory tests, the color-word Stroop task, the Attention Network Test, and a non-linguistic task-switching paradigm. The interpreters did not show advantages in conflict resolution or switching cost where bilingual benefits have been noted. However, an interpretation-specific advantage emerged on the mixing cost in the task-switching paradigm. Additionally, the interpreters had larger verbal and spatial memory spans. Interpreters do not continue to garner benefits from bilingualism, but they do appear to possess benefits specific to their experience with simultaneous interpretation.