Shyness in children is a phenomenon often overlooked as a trait that every child will “grow out of” or stigmatized as an emotional or behavioral anomaly, by caregivers as well as teachers. Yet, academic research on supporting shy children in the context of library youth services is scarce.Unlike social anxiety or introversion, shyness is a lay term that is more difficult to pinpoint, yet inherently meaningful. Asendorpf defines the term broadly as, “various forms of modest, reserved, wary, inhibited, anxious, or withdrawn behaviors in social situations.” While this may serve as a functioning umbrella for a variety of behaviors, not all children who identify as being shy exemplify all of these behaviors.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is caused by the functional loss of the Fragile X Mental Retardation Protein (FMRP). The estimated prevalence of FXS is 1:2500 males and 1:5000 females. FMRP is an RNA binding protein that is highly expressed in the brain, particularly at the synapse. FMRP is involved in mRNA transport and in the translational regulation of several neuronal mRNAs. The current model is that FMRP binds to specific sequences or structural motifs in mRNAs at the synapse and suppresses their translation. However, the precise mechanism of translational repression by FMRP is unknown. To determine the role of FMRP in FXS and elucidate the mechanism of how FMRP represses translation, we used the Drosophila model system, as flies lacking FMRP exhibit phenotypes observed in FXS. First, we showed with in vitro translation assays that FMRP represses translation of a Renilla luciferase reporter mRNA that does not have G-quadruplex or a pseudoknot forming sequence, which are the previously proposed FMRP-binding elements. Mutational analysis then revealed that the KH1 and RGG domains of FMRP are important for translation repression. Additionally, we developed a fluorescence-based, quantitative assay to monitor the binding of FMRP to the 80S ribosome. We found that FMRP binds with high affinity (KD = 20 ± 3 nM) to the Drosophila 80S ribosome near the 60S large ribosomal subunit protein L5 and this interaction was mRNA- independent. Finally, a cryo-electron microscopic reconstruction of the 80S ribosome·FMRP complex showed that FMRP binds within the inter-subunit space of the ribosomes such that it would block the binding regions of tRNA and translation elongation factors on the ribosome. These findings suggest a novel mechanism in which the binding of FMRP to the ribosome inhibits translation by blocking the docking of essential components of the translational machinery to the ribosome. These studies provide insight into the mechanism of translational control by FMRP and may help in identifying potential therapeutic approaches for treating FXS

Translational control is a common mechanism used to regulate gene expression and occur in bacteria to mammals. Typically in translational control, an RNA-binding protein binds to a unique sequence in the mRNA to regulate protein synthesis by the ribosomes. Alternatively, a protein may bind to or modify a translation factor to globally regulate protein synthesis by the cell. Here, we review translational control by the fragile X mental retardation protein (FMRP), the absence of which causes the neurological disease, fragile X syndrome (FXS).

Objective

In 2002, the National Library of Medicine (NLM) introduced semi-automated indexing of Medline using the Medical Text Indexer (MTI). In 2021, NLM announced that it would fully automate its indexing in Medline with an improved MTI by mid-2022. This pilot study examines indexing using a sample of records in Medline from 2000, and how an early, public version of MTI's outputs compares to records created by human indexers.

Methods

This pilot study examines twenty Medline records from 2000, a year before the MTI was introduced as a MeSH term recommender. We identified twenty higher- and lower-impact biomedical journals based on Journal Impact Factor (JIF) and examined the indexing of papers by feeding their PubMed records into the Interactive MTI tool.

Results

In the sample, we found key differences between automated and human-indexed Medline records: MTI assigned more terms and used them more accurately for citations in the higher JIF group, and MTI tended to rank the Male check tag more highly than the Female check tag and to omit Aged check tags. Sometimes MTI chose more specific terms than human indexers but was inconsistent in applying specificity principles.

Conclusion

NLM's transition to fully automated indexing of the biomedical literature could introduce or perpetuate inconsistencies and biases in Medline. Librarians and searchers should assess changes to index terms, and their impact on PubMed's mapping features for a range of topics. Future research should evaluate automated indexing as it pertains to finding clinical information effectively, and in performing systematic searches.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused by loss of function of the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is involved in the translational regulation of several neuronal mRNAs. However, the precise mechanism of translational inhibition by FMRP is unknown. Here, we show that FMRP inhibits translation by binding directly to the L5 protein on the 80S ribosome. Furthermore, cryoelectron microscopic reconstruction of the 80S ribosome⋅FMRP complex shows that FMRP binds within the intersubunit space of the ribosome such that it would preclude the binding of tRNA and translation elongation factors on the ribosome. These findings suggest that FMRP inhibits translation by blocking the essential components of the translational machinery from binding to the ribosome.