Detection of a Subset of Posttranscriptional Transfer RNA Modifications in Vivo with a Restriction Fragment Length Polymorphism-Based Method

Transfer RNAs (tRNAs) are among the most heavily modified RNA species. Posttranscriptional tRNA modifications (ptRMs) play fundamental roles in modulating tRNA structure and function and are being increasingly linked to human physiology and disease. Detection of ptRMs is often challenging, expensive, and laborious. Restriction fragment length polymorphism (RFLP) analyses study the patterns of DNA cleavage after restriction enzyme treatment and have been used for the qualitative detection of modified bases on mRNAs. It is known that some ptRMs induce specific and reproducible base “mutations” when tRNAs are reverse transcribed. For example, inosine, which derives from the deamination of adenosine, is detected as a guanosine when an inosine-containing tRNA is reverse transcribed, amplified via polymerase chain reaction (PCR), and sequenced. ptRM-dependent base changes on reverse transcription PCR amplicons generated as a consequence of the reverse transcription reaction might create or abolish endonuclease restriction sites. The suitability of RFLP for the detection and/or quantification of ptRMs has not been studied thus far. Here we show that different ptRMs can be detected at specific sites of different tRNA types by RFLP. For the examples studied, we show that this approach can reliably estimate the modification status of the sample, a feature that can be useful in the study of the regulatory role of tRNA modifications in gene expression

Repealing Ireland's Eighth Amendment: abortion rights and democracy today

In 2018, the Irish public voted to repeal the Eighth Amendment to the Irish Constitution, which since 1983 banned abortion in the country. While this was a watershed moment in Irish history, it was not unconnected to wider discussions now taking place around the world concerning gender, reproductive rights, the future of religion, Church–State relationships, democracy and social movements. With this Forum, we want to prompt some anthropological interpretations of Ireland's repeal of the Eighth Amendment as a matter concerning not only reproductive rights, but also questions of life and death, faith and shame, women and men, state power and individual liberty, and more. We also ask what this event might mean (if anything) for other societies dealing with similar issues

Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential

Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye's incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye-wheat introgressions.Peer reviewe

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Writing Anthropology

Writing is key in anthropology, as one of its main modes of communication. Teaching, research, publications, and outreach all build on, or consist of, writing. This entry traces how anthropological writing styles have evolved over time according to changing politics in the discipline. It starts out in the late nineteenth century, showing how early writings in the discipline aimed to be objective. While writing anthropology in a literary mode goes a long way back, it was not until the 1970s that writing began to be collectively acknowledged as a craft to be cultivated in the discipline. This led to a boom of experimental ethnographic writing from the 1980s, as part of the ‘writing culture’ debate. The idea behind experimental narratives was that they might convey social life more accurately than conventional academic writing. Today, literary production and culture continue to be a source of inspiration for anthropologists, as well as a topic of study. Anthropological writing ranges from creative nonfiction to memoirs, journalism, and travel writing. Writing in such non-academic genres can be a way to make anthropological approaches and findings more widely known, and can inspire academic writing to become more accessible. Recent developments in anthropological writings include collaborative text production with interlocutors and artists. However, the tendency for experimentation is also held in check, as publishing in academic publication formats and featuring in citation indices is crucial for anthropologists’ careers. Still, as our writing moves increasingly online, there is a growth of flexible formats for publishing, including online books, essays on current affairs, and conversations in journals.The Cambridge Encyclopedia of Anthropology (CEA) is an open-access teaching and learning resource.</p

Introducing the Anthropologist as Writer : Across and Within Genres

Taking existing conversations in anthropology as a point of departure, the mission of this volume is twofold: first, to identify different writing genres that anthropologists actually engage with; second, to argue for the usefulness and necessity for anthropologists of taking  writing as a craft seriously and of writing across and within genres in new ways. This introductory chapter contextualizes anthropological writing historically and theoretically, moves on to my own experience of writing cultural (dance) journalism as one instance of broadening anthropological writing, and concludes by offering an overview of ways of writing anthropology as discussed in the following chapters: in relation to the making of an anthropological career, ethnographic writing, journalistic and popular writing, and writing across genres.