The emerging roles of deubiquitinases in plant proteostasis.

Proper regulation of protein homeostasis (proteostasis) is essential for all organisms to survive. A diverse range of post-translational modifications (PTMs) allow precise control of protein abundance, function and cellular localisation. In eukaryotic cells, ubiquitination is a widespread, essential PTM that regulates most, if not all cellular processes.

Mechanosensory trichome cells evoke a mechanical stimuli-induced immune response in Arabidopsis thaliana.

Perception of pathogen-derived ligands by corresponding host receptors is a pivotal strategy in eukaryotic innate immunity. In plants, this is complemented by circadian anticipation of infection timing, promoting basal resistance even in the absence of pathogen threat. Here, we report that trichomes, hair-like structures on the epidermis, directly sense external mechanical forces, including raindrops, to anticipate pathogen infections in Arabidopsis thaliana.

Suppression of MYC transcription activators by the immune cofactor NPR1 fine-tunes plant immune responses.

Plants tailor immune responses to defend against pathogens with different lifestyles. In this process, antagonism between the immune hormones salicylic acid (SA) and jasmonic acid (JA) optimizes transcriptional signatures specifically to the attacker encountered. Antagonism is controlled by the transcription cofactor NPR1.

Characterising Plant Deubiquitinases with Activity-based Labelling and Ubiquitin Chain Disassembly Assays.

Post-translational modification of proteins by ubiquitin is an essential cellular signaling mechanism in all eukaryotes. Ubiquitin is removed from target proteins by a wide range of deubiquitinase (DUB) enzymes with different activities and substrate specificities. Understanding how DUBs function is a vital first step to uncovering their cellular roles.

Dynamic ubiquitination determines transcriptional activity of the plant immune coactivator NPR1.

Activation of systemic acquired resistance in plants is associated with transcriptome reprogramming induced by the unstable coactivator NPR1. Immune-induced ubiquitination and proteasomal degradation of NPR1 are thought to facilitate continuous delivery of active NPR1 to target promoters, thereby maximising gene expression. Because of this potentially costly sacrificial process, we investigated if ubiquitination of NPR1 plays transcriptional roles prior to its proteasomal turnover.

A role for S-nitrosylation of the SUMO-conjugating enzyme SCE1 in plant immunity.

SUMOylation, the covalent attachment of the small ubiquitin-like modifier (SUMO) to target proteins, is emerging as a key modulator of eukaryotic immune function. In plants, a SUMO1/2-dependent process has been proposed to control the deployment of host defense responses. The molecular mechanism underpinning this activity remains to be determined, however.

Transcriptional regulation by complex interplay between post-translational modifications.

Transcriptional reprogramming in response to developmental changes or environmental inputs is regulated by a wide variety of transcription factors and cofactors. In plants, the stability of many transcriptional regulators is mediated by the ubiquitin-mediated proteasome. Recent reports suggest that additional post-translational modifications modulate the ubiquitination and thus stability of transcriptional regulators.

Nitric oxide and S-nitrosoglutathione function additively during plant immunity.

Nitric oxide (NO) is emerging as a key regulator of diverse plant cellular processes. A major route for the transfer of NO bioactivity is S-nitrosylation, the addition of an NO moiety to a protein cysteine thiol forming an S-nitrosothiol (SNO). Total cellular levels of protein S-nitrosylation are controlled predominantly by S-nitrosoglutathione reductase 1 (GSNOR1) which turns over the natural NO donor, S-nitrosoglutathione (GSNO).

2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 3--LBA, biomarkers and immunogenicity).

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5 day, week-long event - A Full Immersion Bioanalytical Week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS and LBA approaches, including the focus on biomarkers and immunogenicity.

2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 2 - hybrid LBA/LCMS and input from regulatory agencies).

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity.

2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 1 - small molecules by LCMS).

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity.

Workshop report: Crystal City V--quantitative bioanalytical method validation and implementation: the 2013 revised FDA guidance.

In September 2013, the FDA released a draft revision of the Bioanalytical Method Validation (BMV) Guidance, which included a number of changes to the expectations for bioanalysis, most notably the inclusion of biomarker assays and data. To provide a forum for an open, inclusive discussion of the revised draft BMV Guidance, the AAPS and FDA once again collaborated to convene a two-and-a-half day workshop during early December 2013 in Baltimore, MD, USA. The resulting format embodied extensive open discussion and each thematic session included only brief, concise descriptions by Agency and industry representatives prior to opening the floor discussion.

S-nitrosothiols regulate nitric oxide production and storage in plants through the nitrogen assimilation pathway.

Nitrogen assimilation plays a vital role in plant metabolism. Assimilation of nitrate, the primary source of nitrogen in soil, is linked to the generation of the redox signal nitric oxide (NO). An important mechanism by which NO regulates plant development and stress responses is through S-nitrosylation, that is, covalent attachment of NO to cysteine residues to form S-nitrosothiols (SNO).

Synthesis of redox-active molecules and their signaling functions during the expression of plant disease resistance.

Significance: Activation of immune responses in plants is associated with a parallel burst of both reactive oxygen intermediates (ROIs) and nitric oxide (NO). The mechanisms by which these small redox-active molecules are synthesized and their signaling functions are critical for plants to defend themselves against pathogen infection.

Recent Advances: The synthesis of apoplastic ROIs by plants after pathogen recognition has long been attributed to membrane-bound NAPDH oxidases.

Herpes simplex virus-1 encephalitis: a review of current disease management with three case reports.

Herpes simplex virus-1 (HSV-1) is the most common cause of lethal sporadic encephalitis. Despite improved therapy with intraveneous acyclovir, HSV-1 encephalitis is associated with persistent severe neurological deficits. We report three cases of adult patients with HSV-1 encephalitis (HSE), discuss the current accepted guidelines for treatment as published by the Infectious Disease Society of America (IDSA) and review the literature pertaining to HSE.

S-adenosylmethionine levels in the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection.

Background: S-adenosylmethionine (AdoMet) is a key molecule involved in methylation reactions and polyamine synthesis. Pneumocystis carinii are unable to synthesize this molecule and have been shown to scavenge this metabolic intermediate from the plasma of rats during active infection. A prior study involving humans strongly suggested that low levels of plasma AdoMet are sensitive and specific indicators of acute infection.

Signal detection theory analyses of semantic priming in word recognition.

Word recognition, semantic priming, and cognitive impenetrability research have used signal detection theory (SDT) measures to separate perceptual and postperceptual processes. In the D. Norris (1986) checking model and model simulation (D.

"Nonparametric" A' and other modern misconceptions about signal detection theory.

Many modern descriptions of signal detection theory (SDT) are, at best, distorted caricatures of the Gaussian equal-variance model of SDT (G-SDT). The distortions have sometimes led to important, but unwarranted, conclusions about the nature of cognitive processes. Some researchers reject using d' and beta because of concerns about the validity of explicit underlying assumptions (that are shared with most inferential statistics), instead using either the supposedly "nonparametric" measures of A' and B" or measures known to confound ability and bias.

Exterior letters are not privileged in the early stage of visual word recognition during reading: comment on Jordan, Thomas, Patching and Scott-Brown (2003).

Potential sources for the discrepancy between the letter position effects in T. R. Jordan, S.