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1.  Partitioning, repressing and derepressing: dynamic regulations in MLA immune receptor triggered defense signaling 
Plants and animals have evolved intracellular nucleotide-binding domain and leucine-rich repeat-containing immune receptors (NLRs) to perceive non-self and trigger immune responses. Plant NLRs detect strain-specific pathogen effectors and activate immune signaling leading to extensive transcriptional reprogramming and termination of pathogen infection. Here we review the recent findings in barley MLA immune receptor mediated immune responses against the barley powdery mildew fungus. We focus on nucleocytoplasmic partitioning of immune receptor, bifurcation of immune signaling, transcriptional repression and derepression connecting receptor activation to immune responses. We also discuss similar findings from other plant NLRs where appropriate.
doi:10.3389/fpls.2013.00396
PMCID: PMC3792363  PMID: 24115952
plant NLRs; MLA; barley; cell death; immune signaling; transcription factors; transcription regulation
2.  Memory and Executive Screening (MES): a brief cognitive test for detecting mild cognitive impairment 
BMC Neurology  2012;12:119.
Background
Mild cognitive impairment (MCI), defined as a transitional zone between normal cognition and dementia, requires a battery of formal neuropsychological tests administered by a trained rater for its diagnosis. The objective of this study was to develop a screening tool for MCI.
Methods
One hundred ninety seven cognitively normal controls (NC), one hundred sixteen patients with amnestic MCI –single domain (aMCI-sd), one hundred ninety five patients with amnestic MCI-multiple domain (aMCI-md), and two hundred twenty eight patients with mild Alzheimer’s disease (AD) were evaluated by comprehensive neuropsychological tests and by the Memory and Executive Screening (MES).
Results
Correlation analysis showed that the three indicators of the MES were significantly negatively related with age (P<0.05), yet not related with education (P>0.05). There was no ceiling or floor effect. Test completion averaged seven minutes (421.14±168.31 seconds). The receiver operating characteristics (ROC) analyses performed on the aMCI-sd group yielded 0.89 for the area under the curve (AUC) (95% CI, 0.85–0.92) for the MES-total score, with sensitivity of 0.795 and specificity of 0.828. There was 81% correct classification rate when the cut-off was set at less than 75. Meanwhile, the aMCI-md group yielded 0.95 for the AUC (95% CI, 0.93–0.97) for the MES-total score, with sensitivity of 0.87 and specificity of 0.91, and 90% correct classification rate when the cut-off was set at less than 72.
Conclusion
The MES, minimally time-consuming, may be a valid and easily administered cognitive screening tool with high sensitivity and specificity for aMCI, with single or multiple domain impairment.
doi:10.1186/1471-2377-12-119
PMCID: PMC3492138  PMID: 23050770
Mild cognitive impairment (MCI); Amnestic MCI-single domain (aMCI-sd); Amnestic MCI-multiple domain (aMCI-md); Alzheimer’s disease (AD); Memory and Executive Screening (MES); Mini-Mental State Examination (MMSE)
3.  Structure-Function Analysis of Barley NLR Immune Receptor MLA10 Reveals Its Cell Compartment Specific Activity in Cell Death and Disease Resistance 
PLoS Pathogens  2012;8(6):e1002752.
Plant intracellular immune receptors comprise a large number of multi-domain proteins resembling animal NOD-like receptors (NLRs). Plant NLRs typically recognize isolate-specific pathogen-derived effectors, encoded by avirulence (AVR) genes, and trigger defense responses often associated with localized host cell death. The barley MLA gene is polymorphic in nature and encodes NLRs of the coiled-coil (CC)-NB-LRR type that each detects a cognate isolate-specific effector of the barley powdery mildew fungus. We report the systematic analyses of MLA10 activity in disease resistance and cell death signaling in barley and Nicotiana benthamiana. MLA10 CC domain-triggered cell death is regulated by highly conserved motifs in the CC and the NB-ARC domains and by the C-terminal LRR of the receptor. Enforced MLA10 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that MLA10 activity in cell death signaling is suppressed in the nucleus but enhanced in the cytoplasm. By contrast, nuclear localized MLA10 is sufficient to mediate disease resistance against powdery mildew fungus. MLA10 retention in the cytoplasm was achieved through attachment of a glucocorticoid receptor hormone-binding domain (GR), by which we reinforced the role of cytoplasmic MLA10 in cell death signaling. Together with our data showing an essential and sufficient nuclear MLA10 activity in disease resistance, this suggests a bifurcation of MLA10-triggered cell death and disease resistance signaling in a compartment-dependent manner.
Author Summary
Plants utilize a multilayered immune system to protect themselves against pathogens. One layer of innate immunity is controlled by intracellular immune receptors called disease resistance (R) proteins. Plant R proteins are powerful molecules capable of triggering host cell suicide thereby restricting pathogen growth. Therefore, it is crucial for plants to control R protein activity in signaling cell death to avoid harmful autoimmune responses. The Barley MLA locus encodes a number of immune receptors that each recognizes a specific powdery mildew fungal strain. Upon pathogen recognition MLAs trigger host defenses concomitant with a rapid cell death response. We here show that MLA10 cell death-inducing activity is tightly regulated by conserved motifs located in two of its domains and by specific cellular chaperone components. Furthermore, we show distinct functions for the nuclear and cytoplasmic MLA10 pools in disease resistance and cell death signaling and provide evidence for a model uncoupling MLA10 cell death signaling from its disease resistance activity. Our results suggest that plant immune receptors integrate signals from multiple sub-cellular compartments to coordinate effective immune responses against pathogen attack.
doi:10.1371/journal.ppat.1002752
PMCID: PMC3369952  PMID: 22685408
4.  Occupational Solvent Exposure and Brain Function: An fMRI Study 
Environmental Health Perspectives  2011;119(7):908-913.
Background: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown.
Objectives: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers.
Methods: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure.
Results: Solvent-exposed workers’ performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices—areas serving working memory function and attention—was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers.
Conclusions: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.
doi:10.1289/ehp.1002529
PMCID: PMC3222975  PMID: 21296712
brain function; fMRI; solvent exposure
5.  Occupational Exposure to Organic Solvents during Bridge Painting 
Annals of Occupational Hygiene  2010;54(4):417-426.
Exposure to volatile organic compounds (VOCs) from bridge painting was measured in New York City and New Jersey during the summer and fall seasons from 2005 to 2007. The effect of painting activities (paint coating layer, confinement setup, and application method) and meteorological conditions (temperature, humidity, and wind speed) on solvent exposure to aromatic, ketone, ester, and alkane compounds were individually evaluated. Mixed-effect models were used to examine the combination effects of these factors on the air concentration of total VOCs as the individual compound groups were not present in all samples. Air concentration associated with spraying was not affected by meteorological conditions since spraying was done in a confined space, thus reducing their impact on solvent air concentration. The mixed models for brushing and rolling samples included two fixed factors, i.e. application method and temperature, and one random factor, i.e. sampling day. An independent dataset (daily air samples) was used to validate the mixed model constructed for brushing and rolling samples. The regression line of the predicted values and actual measurements had a slope of 1.32 ± 0.15 for daily brushing and rolling samples, with almost all points being within the 95% confidence bands. The constructed model provides practical approaches for estimating the solvent exposure from brushing and rolling activities among construction painters. An adjusted mean air concentration derived from the activity-specific spray samples was the best estimate for that painting application.
doi:10.1093/annhyg/meq021
PMCID: PMC2902363  PMID: 20354053
construction; occupational exposure; oil-based paints; painting; solvents
6.  Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys 
Nature medicine  2005;11(12):1295-1298.
We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans.
doi:10.1038/nm1330
PMCID: PMC3018862  PMID: 16311604
7.  European solvent industry group generic exposure scenario risk and exposure tool 
The European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) was developed to facilitate the safety evaluation of consumer uses of solvents, as required by the European Union Registration, Evaluation and Authorization of Chemicals (REACH) Regulation. This exposure-based risk assessment tool provides estimates of both exposure and risk characterization ratios for consumer uses. It builds upon the consumer portion of the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) tool by implementing refinements described in ECETOC TR107. Technical enhancements included the use of additional data to refine scenario defaults and the ability to include additional parameters in exposure calculations. Scenarios were also added to cover all frequently encountered consumer uses of solvents. The TRA tool structure was modified to automatically determine conditions necessary for safe use. EGRET reports results using specific standard phrases in a format consistent with REACH exposure scenario guidance, in order that the outputs can be readily assimilated within safety data sheets and similar information technology systems. Evaluation of tool predictions for a range of commonly encountered consumer uses of solvents found it provides reasonable yet still conservative exposure estimates.
doi:10.1038/jes.2012.128
PMCID: PMC3941027  PMID: 23361440
consumer; exposure model; exposure scenario; REACH; safety data sheet; ECETOC-TRA

Results 1-7 (7)