Rapid discovery and evolution of orthogonal aminoacyl-tRNA synthetase-tRNA pairs.

A central challenge in expanding the genetic code of cells to incorporate noncanonical amino acids into proteins is the scalable discovery of aminoacyl-tRNA synthetase (aaRS)-tRNA pairs that are orthogonal in their aminoacylation specificity. Here we computationally identify candidate orthogonal tRNAs from millions of sequences and develop a rapid, scalable approach-named tRNA Extension (tREX)-to determine the in vivo aminoacylation status of tRNAs. Using tREX, we test 243 candidate tRNAs in Escherichia coli and identify 71 orthogonal tRNAs, covering 16 isoacceptor classes, and 23 functional orthogonal tRNA-cognate aaRS pairs.

Dominant regulation of long-term allograft survival is mediated by microRNA-142.

Organ transplantation is often lifesaving, but the long-term deleterious effects of combinatorial immunosuppression regimens and allograft failure cause significant morbidity and mortality. Long-term graft survival in the absence of continuing immunosuppression, defined as operational tolerance, has never been described in the context of multiple major histocompatibility complex (MHC) mismatches. Here, we show that miR-142 deficiency leads to indefinite allograft survival in a fully MHC mismatched murine cardiac transplant model in the absence of exogenous immunosuppression.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

Aims: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate.

Radiomic Features of Primary Rectal Cancers on Baseline T -Weighted MRI Are Associated With Pathologic Complete Response to Neoadjuvant Chemoradiation: A Multisite Study.

Background: Twenty-five percent of rectal adenocarcinoma patients achieve pathologic complete response (pCR) to neoadjuvant chemoradiation and could avoid proctectomy. However, pretreatment clinical or imaging markers are lacking in predicting response to chemoradiation. Radiomic texture features from MRI have recently been associated with therapeutic response in other cancers.

Developmental Analysis of Seed Transcriptomes Reveals Functional Gene Expression Clusters and Four Imprinted, Endosperm-Expressed Genes.

The double fertilization of the female gametophyte initiates embryogenesis and endosperm development in seeds the activation of genes involved in cell differentiation, organ patterning, and growth. A subset of genes expressed in endosperm exhibit imprinted expression, and the correct balance of gene expression between parental alleles is critical for proper endosperm and seed development. We use a transcriptional time series analysis to identify genes that are associated with key shifts in seed development, including genes associated with secondary cell wall synthesis, mitotic cell cycle, chromatin organization, auxin synthesis, fatty acid metabolism, and seed maturation.

Progression from Early/Intermediate to Advanced Forms of Age-Related Macular Degeneration in a Large UK Cohort: Rates and Risk Factors.

Purpose: To estimate rates and risk factors for progression to geographic atrophy (GA) or choroidal neovascularization (CNV) among eyes diagnosed with early or intermediate age-related macular degeneration (AMD) in clinical practice.

Design: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database from the United Kingdom.

Participants: Patients aged 50 years or more with diagnosis of early/intermediate AMD in at least 1 eye (the study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR.

Chromosome-Level Assembly of the Genome Reveals Conserved Patterns of Nematode Genome Organization.

The nematode is one of the key model systems in biology, including possessing the first fully assembled animal genome. Whereas is a self-reproducing hermaphrodite with fairly limited within-population variation, its relative is an outcrossing species with much more extensive genetic variation, making it an ideal parallel model system for evolutionary genetic investigations. Here, we greatly improve on previous assemblies by generating a chromosome-level assembly of the entire genome (124.

Echocardiographic assessment of the right heart in adults: a practical guideline from the British Society of Echocardiography.

The structure and function of the right side of the heart is influenced by a wide range of physiological and pathological conditions. Quantification of right heart parameters is important in a variety of clinical scenarios including diagnosis, prognostication, and monitoring response to therapy. Although echocardiography remains the first-line imaging investigation for right heart assessment, published guidance is relatively sparse in comparison to that for the left ventricle.

The Human Oral Microbiome in Health and Disease: From Sequences to Ecosystems.

t: The human oral cavity is home to an abundant and diverse microbial community (i.e., the oral microbiome), whose composition and roles in health and disease have been the focus of intense research in recent years.

Correction: Tissue-Specific Expressed Antibody Variable Gene Repertoires.

[This corrects the article DOI: 10.1371/journal.pone.

Spectroscopic confirmation of a mature galaxy cluster at a redshift of 2.

Galaxy clusters are the most massive virialized structures in the Universe and are formed through the gravitational accretion of matter over cosmic time. The discovery of an evolved galaxy cluster at redshift z = 2, corresponding to a look-back time of 10.4 billion years, provides an opportunity to study its properties.

Embryogenic cell suspensions for high-capacity genetic transformation and regeneration of switchgrass ( L.).

Background: Switchgrass ( L.), a North American prairie grassland species, is a potential lignocellulosic biofuel feedstock owing to its wide adaptability and biomass production. Production and genetic manipulation of switchgrass should be useful to improve its biomass composition and production for bioenergy applications.

Patterns of Hybrid Seed Inviability in the Mimulus guttatus sp. Complex Reveal a Potential Role of Parental Conflict in Reproductive Isolation.

Genomic conflicts may play a central role in the evolution of reproductive barriers. Theory predicts that early-onset hybrid inviability may stem from conflict between parents for resource allocation to offspring. Here, we describe M.

Comparative Safety Profile of the Fixed-Dose Combination Corticosteroid and Long-acting β-Agonist Fluticasone Propionate/Formoterol Fumarate: A 36-Month Longitudinal Cohort Study in UK Primary Care.

Objective: The inhaled corticosteroid/long-acting β-agonist (ICS/LABA) fluticasone propionate/formoterol fumarate (FP/FORM; Flutiform) has been available as fixed-dose combination (FDC) therapy for asthma patients aged ≥ 12 years in the UK since 2012. This post-authorisation safety study examined adverse outcomes and prescribing practices for FP/FORM and other FDC ICS/LABA therapies in a real-life clinical setting over 36 months.

Methods: Historical, longitudinal cohort database study using UK primary care data from the Clinical Practice Research Datalink (CPRD) database, for patients initiated on or switched to an FDC ICS/LABA (ENCePP study number: EUPAS12330).

Ways to harness the built environment of ambulatory cancer facilities for comprehensive patient support: A review of the literature.

Objective: To review patient experiences of the architectural elements conducive to a supportive or healing-promoting environment in the context of ambulatory oncology care.

Design: A comprehensive review of original peer-reviewed qualitative studies conducted to reveal the meaning and significance of patient experience in this context was undertaken.

Data Sources: Studies were identified through electronic databases including Ovid MEDLINE, CINAHL, PubMed and Embase.

A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.

Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts.

Beyond the pipeline: a critique of the discourse surrounding the development of an Indigenous primary healthcare workforce in Australia.

A central strategy in addressing health disparities experienced by Indigenous people has been based on a concern with workforce improvement. In this paper, the Indigenous Australian healthcare workforce literature since 1977 is reviewed and its scope of concern, as being often limited to questions of 'supply', is critiqued. The pipeline metaphor, whether used explicitly or implied, regularly focuses attention on closing the gap on Indigenous representation within the health workforce.

Shearwaters know the direction and distance home but fail to encode intervening obstacles after free-ranging foraging trips.

While displacement experiments have been powerful for determining the sensory basis of homing navigation in birds, they have left unresolved important cognitive aspects of navigation such as what birds know about their location relative to home and the anticipated route. Here, we analyze the free-ranging Global Positioning System (GPS) tracks of a large sample ( = 707) of Manx shearwater, , foraging trips to investigate, from a cognitive perspective, what a wild, pelagic seabird knows as it begins to home naturally. By exploiting a kind of natural experimental contrast (journeys with or without intervening obstacles) we first show that, at the start of homing, sometimes hundreds of kilometers from the colony, shearwaters are well oriented in the homeward direction, but often fail to encode intervening barriers over which they will not fly (islands or peninsulas), constrained to flying farther as a result.

Deep learning algorithm predicts diabetic retinopathy progression in individual patients.

The global burden of diabetic retinopathy (DR) continues to worsen and DR remains a leading cause of vision loss worldwide. Here, we describe an algorithm to predict DR progression by means of deep learning (DL), using as input color fundus photographs (CFPs) acquired at a single visit from a patient with DR. The proposed DL models were designed to predict future DR progression, defined as 2-step worsening on the Early Treatment Diabetic Retinopathy Diabetic Retinopathy Severity Scale, and were trained against DR severity scores assessed after 6, 12, and 24 months from the baseline visit by masked, well-trained, human reading center graders.

From statics of composites to acoustic metamaterials.

The Hashin-Shtrikman formalism for the static response of a composite is first summarized, in a form applicable to anisotropic media and arbitrary two-point correlations. Its extension to dynamic response is then explained and in particular the extra coupling, for stress with velocity as well as strain, and momentum density with strain as well as velocity that inevitably follows, is highlighted. The more recent dynamical formulations which incorporate extra flexibility through the use of a weighted mean displacement also receive mention.

Validation of Glacier Topographic Acquisitions from an Airborne Single-Pass Interferometer.

The airborne glacier and ice surface topography interferometer (GLISTIN-A) is a single-pass radar interferometer developed for accurate high-resolution swath mapping of dynamic ice surfaces. We present the first validation results of the operational sensor, collected in 2013 over glaciers in Alaska and followed by more exhaustive collections from Greenland in 2016 and 2017. In Alaska, overlapping flight-tracks were mosaicked to mitigate potential residual trends across-track and the resultant maps are validated with lidar.

Pellino-1 Regulates Immune Responses to in Models of Inflammatory Lung Disease.

Non-typeable (NTHi) is a frequent cause of lower respiratory tract infection in people with chronic obstructive pulmonary disease (COPD). Pellino proteins are a family of E3 ubiquitin ligases that are critical regulators of TLR signaling and inflammation. The aim of this study was to identify a role for Pellino-1 in airway defense against NTHi in the context of COPD.

Direct Ophthalmic Healthcare Resource Use among Patients with Geographic Atrophy in a Large Cohort from the United Kingdom.

Purpose: To estimate the direct ophthalmic healthcare resource use in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of anonymized data derived from electronic medical records (EMRs) acquired at 10 clinical sites in the United Kingdom.

Participants: Patients aged ≥50 years with ≥1 eye with a clinical record of GA or, for comparison, bilateral early/intermediate AMD.