Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Ribosome profiling and dynamic regulation of translation in mammals

Protein synthesis is an energy-demanding cellular process. Consequently, a well-timed, fine-tuned and plastic regulation of translation is needed to adjust and maintain cell states under dynamically changing environments. Genome-wide monitoring of translation was recently facilitated by ribosome profiling, which uncovered key features of translation regulation. In this review, we summarize recent ribosome profiling studies in mammals providing novel insight in dynamic translation regulation, notably related to circadian rhythms, diurnal feeding/fasting cycles, cell cycle progression, stress responses, and tRNA landscapes. In particular, recent results show that regulating translation initiation and elongation represent important mechanisms used in mammalian cells to rapidly modulate protein expression in dynamically changing environments

Ribo-DT: An automated pipeline for inferring codon dwell times from ribosome profiling data

Protein synthesis is an energy consuming process characterised as a pivotal and highly regulated step in gene expression. The net protein output is dictated by a combination of translation initiation, elongation and termination rates that have remained difficult to measure. Recently, the development of ribosome profiling has enabled the inference of translation parameters through modelling, as this method informs on the ribosome position along the mRNA. Here, we present an automated, reproducible and portable computational pipeline to infer relative single-codon and codon-pair dwell times as well as gene flux from raw ribosome profiling sequencing data. As a case study, we applied our workflow to a publicly available yeast ribosome profiling dataset consisting of 57 independent gene knockouts related to RNA and tRNA modifications. We uncovered the effects of those modifications on translation elongation and codon selection during decoding. In particular, knocking out mod5 and trm7 increases codon-specific dwell times which indicates their potential tRNA targets, and highlights effects of nucleotide modifications on ribosome decoding rate

Lines 1352-1449, Regiment of Princes Collation Tables Group MITCH 4

Files in this work belong to a collection of handwritten variant tables compiled by Charles Blyth and a team consisting of David Greetham, Jerome Mitchell, Gail Sigal, Peter Farley, Marcia Marzec, and David Yerkes during the 1980s and 1990s to collate the manuscripts of Thomas Hoccleve's fifteenth-century poem, 'The Regiment of Princes.' Blyth used these tables to help produce his 1999 edition of the poem published by TEAMS. Blyth passed this collection to Elon Lang in 2009. Lang set up the Hoccleve Archive in 2012 at UT-Austin to preserve and publish the collation tables, to collect other materials related to Hoccleve and Hoccleve scholarship, and to develop strategies for building and using digital archives and editions.Digital images of the variant collation tables in this work were produced by UTAustin Liberal Arts ITS staff member Emma Whelan, Rebecca van Kniest, and members of the UT-School of Information Fall 2012 Digitization Methods class when their names are included in a dc.contributer field. Tables are identified in the title field by a line number range from Blyth's edition of 'The Regiment of Princes.' Transcriptions of marginal glosses associated with some lines in the source manuscripts are written on verso sides of these collation tables or on subsequent sheets. Images of these versos or subsequent sheets are identified by suffices appended to the 'table0000' filename.Humanitie

Pancreatic α- and β-Cellular Clocks Have Distinct Molecular Properties and Impact on Islet Hormone Secretion and Gene Expression

A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets and did not explore the interplay between α-cell and β-cell clocks. We performed a parallel analysis of the molecular properties of α-cell and β-cell oscillators using a mouse model expressing three reporter genes: one labeling α cells, one specific for β cells, and a third monitoring circadian gene expression. Thus, phase entrainment properties, gene expression, and functional outputs of the α-cell and β-cell clockworks could be assessed in vivo and in vitro at the population and single-cell level. These experiments showed that α-cellular and β-cellular clocks are oscillating with distinct phases in vivo and in vitro. Diurnal transcriptome analysis in separated α and β cells revealed that a high number of genes with key roles in islet physiology, including regulators of glucose sensing and hormone secretion, are differentially expressed in these cell types. Moreover, temporal insulin and glucagon secretion exhibited distinct oscillatory profiles both in vivo and in vitro. Altogether, our data indicate that differential entrainment characteristics of circadian α-cell and β-cell clocks are an important feature in the temporal coordination of endocrine function and gene expression

PGC1α and exercise adaptations in zebrafish

Fish species display huge differences in physical activity ranging from lethargy to migration of thousands of miles, making them an interesting model to identify determinants of physical fitness. Here, we show a remarkable plasticity of zebrafish in response to exercise and induction of PGC1α (encoded by PPARGC1A), a dominant regulator of mitochondrial biogenesis. Forced expression of human PPARGC1A induces mitochondrial biogenesis, an exercise-like gene expression signature, and physical fitness comparable to wild-type animals trained in counter-current swim tunnels. Quantifying transcriptional and proteomic changes in response to exercise or PGC1α, we identify conserved ‘exercise’ adaptations, including a stoichiometric induction of the electron transport chain (ETC) that re-organizes into respiratory supercomplexes in both conditions. We further show that ndufa4/ndufa4l, previously assigned to complex I, associates to free and supramolecular complex IV in vivo. Thus, zebrafish is a useful and experimentally tractable vertebrate model to study exercise biology, including ETC expression and assembly