The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana.

Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific "avirulent" pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood.

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis.

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet.

Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City.

Norway rats (Rattus norvegicus) are globally distributed and concentrate in urban environments, where they live and feed in closer proximity to human populations than most other mammals. Despite the potential role of rats as reservoirs of zoonotic diseases, the microbial diversity present in urban rat populations remains unexplored. In this study, we used targeted molecular assays to detect known bacterial, viral, and protozoan human pathogens and unbiased high-throughput sequencing to identify novel viruses related to agents of human disease in commensal Norway rats in New York City.

Recombinant production of functional full-length and truncated human TRAM/TICAM-2 adaptor protein involved in Toll-like receptor and interferon signaling.

TRAM/TICAM-2 is used by Toll-like receptor 4 (TLR4) as a bridging adaptor during the mammalian innate immune response. It recruits TRIF, another TIR domain-containing adaptor protein, to TLR4 via TIR domain interactions, which leads to the activation of transcription factors responsible for the production of type-1 interferon and cytokines. The molecular mechanisms of these dual interactions mediated by the TRAM TIR domain are not clear.

Regional, annual, and individual variations in the dihydroxyacetone content of the nectar of ma̅nuka (Leptospermum scoparium) in New Zealand.

A method was designed and validated for the analysis of dihydroxyacetone in the floral nectar of ma̅nuka (Leptospermum scoparium). The method was applied to samples collected from different regions of the North Island and the Nelson region of the upper South Island of New Zealand during the period 2009-2012 as well as to nectar samples from some Australian Leptospermum species. The ratio of dihydroxyacetone to total sugar (DHA/Tsugar) was classified as low (<0.

Acidovorax oryzae catheter-associated bloodstream infection.

Acidovorax oryzae is a bacterium that has never before been reported as pathogenic in human subjects. Here we describe the first case of a successfully treated A. oryzae catheter-associated bloodstream infection in an immunocompetent patient prior to heart transplantation.

Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study.

Background: Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation.

Methods: All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation.

Sea level: measuring the bounding surfaces of the ocean.

The practical need to understand sea level along the coasts, such as for safe navigation given the spatially variable tides, has resulted in tide gauge observations having the distinction of being some of the longest instrumental ocean records. Archives of these records, along with geological constraints, have allowed us to identify the century-scale rise in global sea level. Additional data sources, particularly satellite altimetry missions, have helped us to better identify the rates and causes of sea-level rise and the mechanisms leading to spatial variability in the observed rates.

Site-specific modification of the anticancer and antituberculosis polyether salinomycin by biosynthetic engineering.

The complex bis-spiroacetal polyether ionophore salinomycin has been identified as a uniquely selective agent against cancer stem cells and is also strikingly effective in an animal model of latent tuberculosis. The basis for these important activities is unknown. We show here that deletion of the salE gene abolishes salinomycin production and yields two new analogues, in both of which the C18C19 cis double bond is replaced by a hydroxy group stereospecifically located at C19, but which differ from each other in the configuration of the bis-spiroacetal.

Personalized diagnosis and management of congenital cataract by next-generation sequencing.

Purpose: To assess the utility of integrating genomic data from next-generation sequencing and phenotypic data to enhance the diagnosis of bilateral congenital cataract (CC).

Design: Evaluation of diagnostic technology.

Participants: Thirty-six individuals diagnosed with nonsyndromic or syndromic bilateral congenital cataract were selected for investigation through a single ophthalmic genetics clinic.

Rationale and study design of the REM-HF study: remote management of heart failure using implanted devices and formalized follow-up procedures.

Aims: We wish to assess the clinical and cost-effectiveness of remote monitoring of heart failure patients with cardiac implanted electronic devices.

Methods: REM-HF is a multicentre, randomized, non-blinded, parallel trial designed to compare weekly remote monitoring-driven management with usual care for patients with cardiac implanted electronic devices (ICD, CRT-D, or CRT-P). The trial is event driven, and the final analysis will be performed when 546 events have been observed or the study is terminated at the interim analysis.

Perioperative outcomes of cytoreductive nephrectomy in the UK in 2012.

Objectives: To define the perioperative morbidity and 30-day mortality of cytoreductive nephrectomy (CN) using the British Association of Urological Surgeons (BAUS) nephrectomy dataset for 2012, the first year of public reporting of individual surgeon outcomes in the UK.

Patients And Methods: All nephrectomies recorded in the database in 2012 were analysed, and cytoreductive cases identified. Outcome measures were: blood loss of >1000 mL, transfusion requirement, intra- and postoperative complications assessed by Clavien-Dindo score, and 30-day mortality (including failure-to-rescue rate).

The Academy for Future Science Faculty: randomized controlled trial of theory-driven coaching to shape development and diversity of early-career scientists.

Background: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level.

Virome analysis of Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis ticks reveals novel highly divergent vertebrate and invertebrate viruses.

Unlabelled: A wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored. In the United States, Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis are among the principal tick species associated with pathogen transmission. We used high-throughput sequencing to characterize the viromes of these tick species and identified the presence of Powassan virus and eight novel viruses.

Structural basis for assembly and function of a heterodimeric plant immune receptor.

Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate.

Acute kidney injury in urology patients: incidence, causes and outcomes.

Background: Acute kidney injury (AKI) is common in hospitalised patients and is associated with high mortality rates. However, the epidemiology of AKI in urology patients may differ due to a higher proportion of post-renal causes and surgical procedures that result in the intentional removal of renal parenchyma.

Objectives: We performed a study to examine the incidence, aetiology and outcomes of AKI in a urological population.

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response.

Total synthesis of the antimitotic marine macrolide (-)-leiodermatolide.

Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.

Supplementation of nicotinic acid with NAMPT inhibitors results in loss of in vivo efficacy in NAPRT1-deficient tumor models.

Nicotinamide adenine dinucleotide (NAD) is a metabolite essential for cell survival and generated de novo from tryptophan or recycled from nicotinamide (NAM) through the nicotinamide phosphoribosyltransferase (NAMPT)-dependent salvage pathway. Alternatively, nicotinic acid (NA) is metabolized to NAD through the nicotinic acid phosphoribosyltransferase domain containing 1 (NAPRT1)-dependent salvage pathway. Tumor cells are more reliant on the NAMPT salvage pathway making this enzyme an attractive therapeutic target.

Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft vasculopathy.

Objectives: This study sought to evaluate the diagnostic performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting cardiac allograft vasculopathy (CAV) using contemporary invasive epicardial artery and microvascular assessment techniques as reference standards, and to compare the performance of CMR with that of angiography.

Background: CAV continues to limit the long-term survival of heart transplant recipients. Coronary angiography has a Class I recommendation for CAV surveillance and annual or biannual surveillance angiography is performed routinely in most centers.

Should we consider patients with coexistent hepatitis B or C infection for orthotopic heart transplantation?

Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear.

The distribution of different classes of nuclear localization signals (NLSs) in diverse organisms and the utilization of the minor NLS-binding site inplantnuclear import factor importin-α.

The specific recognition between the import receptor importin-α and the nuclear localization signals (NLSs) is crucial to ensure the selective transport of cargoes into the nucleus. NLSs contain 1 or 2 clusters of positively charged amino acids, which usually bind to the major (monopartite NLSs) or both minor and major NLS-binding sites (bipartite NLSs). In our recent study, we determined the structure of importin-α1a from rice (Oryza sativa), and made 2 observations that suggest an increased utilization of the minor NLS-binding site in this protein.