A Variable Polyglutamine Repeat Affects Subcellular Localization and Regulatory Activity of a Populus ANGUSTIFOLIA Protein.

Polyglutamine (polyQ) stretches have been reported to occur in proteins across many organisms including animals, fungi and plants. Expansion of these repeats has attracted much attention due their associations with numerous human diseases including Huntington's and other neurological maladies. This suggests that the relative length of polyQ stretches is an important modulator of their function. Here, we report the identification of a Populus C-terminus binding protein (CtBP) ANGUSTIFOLIA (PtAN1) which contains a polyQ stretch whose functional relevance had not been established. Analysis of 917 resequenced Populus trichocarpa genotypes revealed three allelic variants at this locus encoding 11-, 13- and 15-glutamine residues. Transient expression assays using Populus leaf mesophyll protoplasts revealed that the 11Q variant exhibited strong nuclear localization whereas the 15Q variant was only found in the cytosol, with the 13Q variant exhibiting localization in both subcellular compartments. We assessed functional implications by evaluating expression changes of putative PtAN1 targets in response to overexpression of the three allelic variants and observed allele-specific differences in expression levels of putative targets. Our results provide evidence that variation in polyQ length modulates PtAN1 function by altering subcellular localization

NASA UAS Traffic Management National Campaign Operations across Six UAS Test Sites

NASA's Unmanned Aircraft Systems Traffic Management research aims to develop policies, procedures, requirements, and other artifacts to inform the implementation of a future system that enables small drones to access the low altitude airspace. In this endeavor, NASA conducted a geographically diverse flight test in conjunction with the FAA's six unmanned aircraft systems Test Sites. A control center at NASA Ames Research Center autonomously managed the airspace for all participants in eight states as they flew operations (both real and simulated). The system allowed for common situational awareness across all stakeholders, kept traffic procedurally separated, offered messages to inform the participants of activity relevant to their operations. Over the 3- hour test, 102 flight operations connected to the central research platform with 17 different vehicle types and 8 distinct software client implementations while seamlessly interacting with simulated traffic

RALFL34 regulates formative cell divisions in Arabidopsis pericycle during lateral root initiation

We describe the role of RALFL34 during early events in lateral root development, and demonstrate its specific importance in orchestrating formative cell divisions in the pericycle.In plants, many signalling molecules, such as phytohormones, miRNAs, transcription factors, and small signalling peptides, drive growth and development. However, very few small signalling peptides have been shown to be necessary for lateral root development. Here, we describe the role of the peptide RALFL34 during early events in lateral root development, and demonstrate its specific importance in orchestrating formative cell divisions in the pericycle. Our results further suggest that this small signalling peptide acts on the transcriptional cascade leading to a new lateral root upstream of GATA23, an important player in lateral root formation. In addition, we describe a role for ETHYLENE RESPONSE FACTORs (ERFs) in regulatingRALFL34 expression. Taken together, we put forward RALFL34 as a new, important player in lateral root initiation

Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers

One-fourth of Plasmodium falciparum proteins have asparagine repeats that increase the propensity for aggregation, especially at elevated temperatures that occur routinely in malaria-infected patients. We report that a Plasmodium Asn repeat-containing protein (PFI1155w) formed aggregates in mammalian cells at febrile temperatures, as did a yeast Asn/Gln-rich protein (Sup35). Co-expression of the cytoplasmic P. falciparum heat shock protein 110 (PfHsp110c) prevented aggregation. Human or yeast orthologs were much less effective. All-Asn and all-Gln versions of Sup35 were protected from aggregation by PfHsp110c, suggesting that this chaperone is not limited to handling runs of Asn. PfHsp110c gene knockout parasites were not viable and conditional knockdown parasites died slowly in the absence of protein-stabilizing ligand. When exposed to brief heat shock, these knockdowns were unable to prevent aggregation of PFI1155w or Sup35 and died rapidly. We conclude that PfHsp110c protects the parasite from harmful effects of its asparagine repeat-rich proteome during febrile episodes

Adults miscoded and misdiagnosed as having pneumonia: results from the British Thoracic Society pneumonia audit

A key objective of the British Thoracic Society national community-acquired pneumonia (CAP) audit was to determine the clinical characteristics and outcomes of hospitalised adults given a primary discharge code of pneumonia but who did not fulfil accepted diagnostic criteria for pneumonia. Adults miscoded as having pneumonia (n=1251) were older compared with adults with CAP (n=6660) (median 80 vs 78 years, p<0.001) and had more comorbid disease, significantly fewer respiratory symptoms (fever, cough, dyspnoea, pleuritic pain), more constitutional symptoms (general deterioration, falls) and significantly lower 30-day inpatient mortality (14.3% vs 17.0%, adjusted OR 0.75, p=0.003)

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant’s sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes use of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. The resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance

Predictors of engagement in first-episode psychosis

Engagement with psychiatric services is critical for ensuring successful outcomes in patients experiencing a first episode of psychosis (FEP). However, it is not known how sociodemographic factors and patient beliefs about the causes of mental illness affect engagement. This study explored predictors of engagement in a cohort of 103 FEP patients presenting to an early-intervention service. Beliefs that mental illness is caused by social stress or thinking odd thoughts predicted higher engagement scores. Patients with no qualifications were found to have higher engagement scores than those educated to a higher level. Ethnicity, gender, age and socioeconomic factors were not significantly correlated with engagement scores. Duration of untreated illness (DUI) significantly predicted higher engagement scores, but only for values >1220days. Duration of untreated psychosis (DUP) was not a significant predictor of patient engagement scores. Patient beliefs about the causes of mental illness are an important factor to be taken into consideration and may represent a target of interventions to increase engagement in FEP

Plasmodium falciparum histidine-rich protein II compromises brain endothelial barriers and may promote cerebral malaria pathogenesis

Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system