Mutations in &ggr;-aminobutyric acid (GABA) transaminase genes in plants or <i>Pseudomonas syringae</i> reduce bacterial virulence

Park, Duck Hwan,Mirabella, Rossana,Bronstein, Philip A.,Preston, Gail M.,Haring, Michel A.,Lim, Chun Keun,Collmer, Alan,Schuurink, Robert C. Blackwell Publishing Ltd 2010 The Plant journal Vol.64 No.2

<P>Summary</P><P><I>Pseudomonas syringae</I> pv. <I>tomato</I> DC3000 is a bacterial pathogen of Arabidopsis and tomato that grows in the apoplast. The non-protein amino acid &ggr;-amino butyric acid (GABA) is produced by Arabidopsis and tomato and is the most abundant amino acid in the apoplastic fluid of tomato. The DC3000 genome harbors three genes annotated as <I>gabT</I> GABA transaminases. A DC3000 mutant lacking all three <I>gabT</I> genes was constructed and found to be unable to utilize GABA as a sole carbon and nitrogen source. In complete minimal media supplemented with GABA, the mutant grew less well than wild-type DC3000 and showed strongly reduced expression of <I>hrpL</I> and <I>avrPto</I>, which encode an alternative sigma factor and effector, respectively, associated with the type III secretion system. The growth of the <I>gabT</I> triple mutant was weakly reduced in Arabidopsis ecotype <I>Landberg erecta</I> (L<I>er</I>) and strongly reduced in the L<I>er pop2-1</I> GABA transaminase-deficient mutant that accumulates higher levels of GABA. Much of the ability to grow on GABA-amended minimal media or in Arabidopsis <I>pop2-1</I> leaves could be restored to the <I>gabT</I> triple mutant by expression <I>in trans</I> of just <I>gabT2.</I> The ability of DC3000 to elicit the hypersensitive response (HR) in tobacco leaves is dependent upon deployment of the type III secretion system, and the <I>gabT</I> triple mutant was less able than wild-type DC3000 to elicit this HR when bacteria were infiltrated along with GABA at levels of 1 m<SMALL>M</SMALL> or more. GABA may have multiple effects on <I>P. syringae</I>–plant interactions, with elevated levels increasing disease resistance.</P>

Risk Assessment for Metalworking Fluids and Respiratory Outcomes

Robert M. Park 한국산업안전보건공단 산업안전보건연구원 2019 Safety and health at work Vol.10 No.4

Background: Metalworking fluids (MWFs) are mixtures with inhalation exposures as mists, dusts, and vapors, and dermal exposure in the dispersed and bulk liquid phase. A quantitative risk assessment was performed for exposure to MWF and respiratory disease. Methods: Risks associated with MWF were derived from published studies and NIOSH Health Hazard Evaluations, and lifetime risks were calculated. The outcomes analyzed included adult onset asthma, hypersensitivity pneumonitis, pulmonary function impairment, and reported symptoms. Incidence rates were compiled or estimated, and annual proportional loss of respiratory capacity was derived from crosssectional assessments. Results: A strong healthy worker survivor effect was present. New-onset asthma and hypersensitivity pneumonitis, at 0.1 mg/m3 MWF under continuous outbreak conditions, had a lifetime risk of 45%; if the associated microbiological conditions occur with only 5% prevalence, then the lifetime risk would be about 3%. At 0.1 mg/m3, the estimate of excess lifetime risk of attributable pulmonary impairment was 0.25%, which may have been underestimated by a factor of 5 or more by a strong healthy worker survivor effect. The symptom prevalence associated with respiratory impairment at 0.1 mg/m3 MWF was estimated to be 5% (published studies) and 21% (Health Hazard Evaluations). Conclusion: Significant risks of impairment and chronic disease occurred at 0.1 mg/m3 for MWFs in use mostly before 2000. Evolving MWFs contain new ingredients with uncharacterized long-term hazards.

Author's Response to Letters to the Editor regarding "Risk Assessment for Toluene Diisocyanate and Respiratory Disease Human Studies"

Park, Robert M. Occupational Safety and Health Research Institute 2022 Safety and health at work Vol.13 No.1

Risk Assessment for Metalworking Fluids and Respiratory Outcomes

Park, Robert M. Occupational Safety and Health Research Institute 2019 Safety and health at work Vol.10 No.4

Background: Metalworking fluids (MWFs) are mixtures with inhalation exposures as mists, dusts, and vapors, and dermal exposure in the dispersed and bulk liquid phase. A quantitative risk assessment was performed for exposure to MWF and respiratory disease. Methods: Risks associated with MWF were derived from published studies and NIOSH Health Hazard Evaluations, and lifetime risks were calculated. The outcomes analyzed included adult onset asthma, hypersensitivity pneumonitis, pulmonary function impairment, and reported symptoms. Incidence rates were compiled or estimated, and annual proportional loss of respiratory capacity was derived from cross-sectional assessments. Results: A strong healthy worker survivor effect was present. New-onset asthma and hypersensitivity pneumonitis, at 0.1 mg/㎥ MWF under continuous outbreak conditions, had a lifetime risk of 45%; if the associated microbiological conditions occur with only 5% prevalence, then the lifetime risk would be about 3%. At 0.1 mg/㎥, the estimate of excess lifetime risk of attributable pulmonary impairment was 0.25%, which may have been underestimated by a factor of 5 or more by a strong healthy worker survivor effect. The symptom prevalence associated with respiratory impairment at 0.1 mg/㎥ MWF was estimated to be 5% (published studies) and 21% (Health Hazard Evaluations). Conclusion: Significant risks of impairment and chronic disease occurred at 0.1 mg/㎥ for MWFs in use mostly before 2000. Evolving MWFs contain new ingredients with uncharacterized long-term hazards.

Risk Assessment for Toluene Diisocyanate and Respiratory Disease Human Studies

PARK, Robert M. Occupational Safety and Health Research Institute 2021 Safety and health at work Vol.12 No.2

Background: Toluene diisocyanate (TDI) is a highly reactive chemical that causes sensitization and has also been associated with increased lung cancer. A risk assessment was conducted based on occupational epidemiologic estimates for several health outcomes. Methods: Exposure and outcome details were extracted from published studies and a NIOSH Health Hazard Evaluation for new onset asthma, pulmonary function measurements, symptom prevalence, and mortality from lung cancer and respiratory disease. Summary exposure-response estimates were calculated taking into account relative precision and possible survivor selection effects. Attributable incidence of sensitization was estimated as were annual proportional losses of pulmonary function. Excess lifetime risks and benchmark doses were calculated. Results: Respiratory outcomes exhibited strong survivor bias. Asthma/sensitization exposure response decreased with increasing facility-average TDI air concentration as did TDI-associated pulmonary impairment. In a mortality cohort where mean employment duration was less than 1 year, survivor bias pre-empted estimation of lung cancer and respiratory disease exposure response. Conclusion: Controlling for survivor bias and assuming a linear dose-response with facility-average TDI concentrations, excess lifetime risks exceeding one per thousand occurred at about 2 ppt TDI for sensitization and respiratory impairment. Under alternate assumptions regarding stationary and cumulative effects, one per thousand excess risks were estimated at TDI concentrations of 10 - 30 ppt. The unexplained reported excess mortality from lung cancer and other lung diseases, if attributable to TDI or associated emissions, could represent a lifetime risk comparable to that of sensitization.

Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells in <i>Arabidopsis thaliana</i>

Park, Jin-Sup,Frost, Jennifer M.,Park, Kyunghyuk,Ohr, Hyonhwa,Park, Guen Tae,Kim, Seohyun,Eom, Hyunjoo,Lee, Ilha,Brooks, Janie S.,Fischer, Robert L.,Choi, Yeonhee National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.8

<P>The DEMETER (DME) DNA glycosylase initiates active DNA demethy-lation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana. DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell. Here, we show that, in the male gametophyte, DME expression is limited to the companion cell of sperm, the vegetative cell, and to a narrow window of time: immediately after separation of the companion cell lineage from the germline. We define transcriptional regulatory elements of DME using reporter genes, showing that a small region, which surprisingly lies within the DME gene, controls its expression in male and female companion cells. DME expression from this minimal promoter is sufficient to rescue seed abortion and the aberrant DNA methylome associated with the null dme-2 mutation. Within this minimal promoter, we found short, conserved enhancer sequences necessary for the transcriptional activities of DME and combined predicted binding motifs with published transcription factor binding coordinates to produce a list of candidate upstream pathway members in the genetic circuitry controlling DNA demethylation in gamete companion cells. These data show how DNA demethylation is regulated to facilitate endosperm gene imprinting and potential transgenerational epigenetic regulation, without subjecting the germline to potentially deleterious transposable element demethylation.</P>

Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature

Robert M. Park 한국산업안전보건공단 산업안전보건연구원 2013 Safety and health at work Vol.4 No.3

Exposure to manganese (Mn) is associated with neurobehavioral effects. There is disagreement on whether commonly occurring exposures in welding, ferroalloy, and other industrial processes produce neurologically significant neurobehavioral changes representing parkinsonism. A review of methodological issues in the human epidemiological literature on Mn identified: (1) studies focused on idiopathic Parkinson disease without considering manganism, a parkinsonian syndrome; (2) studies with healthy worker effect bias; (3) studies with problematic statistical modeling; and (4) studies arising from case series derived from litigation. Investigations with adequate study design and exposure assessment revealed consistent neurobehavioral effects and attributable subclinical and clinical signs and symptoms of impairment. Twenty-eight studies show an exposure-response relationship between Mn and neurobehavioral effects, including 11 with continuous exposure metrics and six with three or four levels of contrasted exposure. The effects of sustained low-concentration exposures to Mn are consistent with the manifestations of early manganism, i.e., consistent with parkinsonism. This is compelling evidence that Mn is a neurotoxic chemical and there is good evidence that Mn exposures far below the current US standard of 5.0 mg/m3 are causing impairment.

Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature

Park, Robert M. Occupational Safety and Health Research Institute 2013 Safety and health at work Vol.4 No.3

Exposure to manganese (Mn) is associated with neurobehavioral effects. There is disagreement on whether commonly occurring exposures in welding, ferroalloy, and other industrial processes produce neurologically significant neurobehavioral changes representing parkinsonism. A reviewof methodological issues in the human epidemiological literature onMnidentified: (1) studies focused on idiopathic Parkinson disease without considering manganism, a parkinsonian syndrome; (2) studies with healthy worker effect bias; (3) studies with problematic statistical modeling; and (4) studies arising from case series derived from litigation. Investigations with adequate study design and exposure assessment revealed consistent neurobehavioral effects and attributable subclinical and clinical signs and symptoms of impairment. Twenty-eight studies show an exposure-response relationship between Mn and neurobehavioral effects, including 11 with continuous exposure metrics and six with three or four levels of contrasted exposure. The effects of sustained low-concentration exposures to Mn are consistent with the manifestations of early manganism, i.e., consistent with parkinsonism. This is compelling evidence thatMnis a neurotoxic chemical and there is good evidence that Mn exposures far below the current US standard of $5.0mg/m^3$ are causing impairment.

In Situ Synthesis of ThermochemicallyReduced Graphene Oxide Conducting Nanocomposites

Park, Ok-Kyung,Hahm, Myung Gwan,Lee, Sungho,Joh, Han-Ik,Na, Seok-In,Vajtai, Robert,Lee, Joong Hee,Ku, Bon-Cheol,Ajayan, Pulickel M. American ChemicalSociety 2012 NANO LETTERS Vol.12 No.4

<P>Highly conductive reduced graphene oxide (GO) polymer nano composites are synthesized by a well-organized in situ thermochemical synthesis technique. The surface functionalization of GO was carried out with aryl diazonium salt including 4-iodoaniline to form phenyl functionalized GO (I-Ph-GO). The thermochemically developed reduced, GO (R-I-Ph-GO) has five times higher electrical conductivity (42 000 S/m) than typical reduced GO (R-GO). We also demonstrate a R-I-Ph-GO/polyimide (PI) composites having more than 10(4) times higher conductivity (similar to 1 S/m) compared to a R-GO/PI composites. The electrical resistances of PI composites with R-I-Ph-GO were dramatically dropped under similar to 3% tensile strain. The R-I-Ph-GO/PI composites with electrically sensitive response caused by mechanical strain are expected to have broad implications for nanoelectromechanical systems.</P>

Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype

( Chan Jae Park ),( Moon Young Lee ),( Paul J Park ),( Se Eun Ha ),( Robyn M Berent ),( Robert Fuchs ),( Joseph M Miano ),( Laren S Becker ),( Kenton M Sanders ),( Seung Il Ro ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.4

Background/Aims Smooth muscle cells (SMCs) characteristically express serum response factor (SRF), which regulates their development. The role of SRF in SMC plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is less characterized. Methods We generated SMC-specific Srf knockout mice and characterized the prenatally lethal phenotype using ultrasound biomicroscopy and histological analysis. We used small bowel partial obstruction surgeries and primary cell culture using cell-specific enhanced green fluorescent protein (EGFP) mouse lines to study phenotypic and molecular changes of SMCs by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. Finally we examined SRF change in human rectalprolapse tissue by immunofluorescence. Results Congenital SMC-specific Srf knockout mice died before birth and displayed severe GI and cardiac defects. Partial obstruction resulted in an overall increase in SRF protein expression. However, individual SMCs appeared to gradually lose SRF in the hypertrophic muscle. Cells expressing low levels of SRF also expressed low levels of platelet-derived growth factor receptor alpha (PDGFRalow) and Ki67. SMCs grown in culture recaptured the phenotypic switch from differentiated SMCs to proliferative PDGFRalow cells. The immediate and dramatic reduction of Srf and Myh11 mRNA expression confirmed the phenotypic change. Human rectal prolapse tissue also demonstrated significant loss of SRF expression. Conclusions SRF expression in SMCs is essential for prenatal development of the GI tract and heart. Following partial obstruction, SMCs down-regulate SRF to transition into proliferative PDGFRalow cells that may represent a phenotype responsible for their plasticity. These findings demonstrate that SRF also plays a critical role in the remodeling process following GI injury. (J Neurogastroenterol Motil 2015;21:589-602)