Sexual reproduction is the null hypothesis for life cycles of rust fungi.

Sexual reproduction, mutation, and reassortment of nuclei increase genotypic diversity in rust fungi. Sexual reproduction is inherent to rust fungi, coupled with their coevolved plant hosts in native pathosystems. Rust fungi are hypothesised to exchange nuclei by somatic hybridisation with an outcome of increased genotypic diversity, independent of sexual reproduction. We provide criteria to demonstrate whether somatic exchange has occurred, including knowledge of parental haplotypes and rejection of fertilisation in normal rust life cycles.

Risk assessment for perfluorooctanoic acid (PFOA) in air, blood serum and water: mortality from liver and kidney disease.

BACKGROUND: Cancer and non-cancer associations have been observed with PFAS (perfluoroalkyl and polyfluoroalkyl) substances in the general population, in populations from locally contaminated environments and in exposed workers. METHODS: A quantitative risk assessment on the PFAS substance perfluorooctanoic acid (PFOA) was conducted for six outcomes using two occupational mortality studies that reported sufficient data to estimate exposure-relationships in relation to serum PFOA levels. Excess lifetime mortality risks were calculated using a life table procedure that applies an exposure response to time-dependent PFOA serum levels for a surviving hypothetical population from ages 20 to 85. Both occupational and general population exposures were described as serum levels, and as air and drinking water concentrations. RESULTS: The estimated occupational inhalation concentrations conferring the benchmark one-per-thousand lifetime risk were 0.21 µg/m3 for chronic kidney disease, 1.0 µg/m3 for kidney cancer and (from the two studies) 0.67 and 1.97 µg/m3 for chronic liver disease. Specific excess lifetime risks estimated in the general population at current PFOA serum levels (~ 1 ng/mL) range 1.5-32 per 100 000 which corresponds to drinking water concentrations of less than 10 ppt. CONCLUSION: Over eight outcome risk estimates, the serum PFOA concentrations conferring 1/1000 occupational lifetime risk ranged 44 to 416 ng/mL corresponding to air concentrations ranging 0.21 to 1.99 µg/m3. The analyses provide a preliminary PFOA quantitative risk assessment for liver and kidney disease mortality which, together with reported assessments for several other end-points, would inform policy on PFAS.

Wheat Stem Rust Surveillance Reveals Two New Races of Puccinia graminis f. sp. tritici in South Africa During 2016 to 2020.

Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is an important disease of wheat in South Africa (SA) and is primarily controlled using resistant cultivars. Understanding virulence diversity of Pgt is essential for successful breeding of resistant cultivars. Samples of infected wheat stems were collected across the major wheat-growing regions of SA from 2016 to 2020 to determine the pathogenic variability of Pgt isolates. Seven races were identified from 517 isolates pathotyped. The most frequently found races were 2SA104 (BPGSC + Sr9h,27,Kw) (35% frequency) and 2SA88 (TTKSF + Sr8b) (33%). Race 2SA42 (PTKSK + Sr8b), which was found in 2017, and 2SA5 (BFGSF + Sr9h), identified in 2017, are new races. The Ug99 variant race 2SA42 is similar in its virulence to 2SA107 (PTKST + Sr8b) except for avirulence to Sr24 and virulence to Sr8155B1. Race 2SA5 is closely related in its virulence to existing races that commonly infect triticale. Certain races showed limited geographical distribution. Races 2SA5, 2SA105, and 2SA108 were found only in the Western Cape, whereas 2SA107 and 2SA42 were detected only in the Free State province. The new and existing races were compared using microsatellite (SSR) marker analysis and their virulence on commercial cultivars was also determined. Seedling response of 113 wheat entries against the new races, using 2SA88, 2SA88+9h, 2SA106, and 2SA107 as controls, revealed 2SA107 as the most virulent (67 entries susceptible), followed by 2SA42 (64), 2SA106 (60), 2SA88+9h (59), 2SA88 (25), and 2SA5 (17). Thus, 2SA5 may not pose a significant threat to local wheat production. SSR genotyping revealed that 2SA5 is genetically distinct from all other SA Pgt races.

Risk assessment for conventional diesel exhaust (before 1990) and lung cancer in a cohort of miners.

Diesel exhaust in the latter half of the 20th century has been found to be a lung carcinogen. Conventional diesel emissions continue in the transportation, mining, construction, and farming industries. From the Diesel Exhaust in Miners Study, a public-use dataset was used to calculate the excess lifetime risk of lung cancer associated with diesel exposure (1947-1997). Excess rates of lung cancer mortality associated with respirable elemental carbon (REC) and possible other mining exposures (e.g., oil mists, explosives emissions) were investigated using Poisson regression methods. Lung cancer mortality declined with increasing employment duration while increasing with cumulative REC and non-diesel exposures, suggesting a strong worker survivor effect. Attenuation of the REC effect was observed with increasing cumulative exposure. After adjustment for employment duration, the excess rate ratio for lung cancer mortality was 0.67 (95% CI = 0.35-0.99) for a 10-year lagged exposure to 200 µg/m3 REC, a typical below-ground exposure in the study mines. At exposures of 200, 10, and 1 µg/m3 REC, the estimated excess lifetime risks, respectively, were 119, 43, and 8.7 per thousand. Analysis of an inception cohort hired after dieselization commenced produced smaller and less certain estimates of lifetime risk. From exposures to conventional diesel engine exhaust common in occupational groups in the past, the excess lifetime risk of lung cancer was more than 5%. Ambient REC exposures in the general population were estimated to confer lifetime risks of 0.14 to 14 per thousand, depending on assumptions made.

Mining the Australian Grains Gene Bank for Rust Resistance in Barley.

Global barley production is threatened by plant pathogens, especially the rusts. In this study we used a targeted genotype-by-sequencing (GBS) assisted GWAS approach to identify rust resistance alleles in a collection of 287 genetically distinct diverse barley landraces and historical cultivars available in the Australian Grains Genebank (AGG) and originally sourced from Eastern Europe. The accessions were challenged with seven US-derived cereal rust pathogen races including Puccinia hordei (Ph-leaf rust) race 17VA12C, P. coronata var. hordei (Pch-crown rust) race 91NE9305 and five pathogenically diverse races of P. striiformis f. sp. hordei (Psh-stripe rust) (PSH-33, PSH-48, PSH-54, PSH-72 and PSH-100) and phenotyped quantitatively at the seedling stage. Novel resistance factors were identified on chromosomes 1H, 2H, 4H and 5H in response to Pch, whereas a race-specific QTL on 7HS was identified that was effective only to Psh isolates PSH-72 and PSH-100. A major effect QTL on chromosome 5HL conferred resistance to all Psh races including PSH-72, which is virulent on all 12 stripe rust differential tester lines. The same major effect QTL was also identified in response to leaf rust (17VA12C) suggesting this locus contains several pathogen specific rust resistance genes or the same gene is responsible for both leaf rust and stripe rust resistance. Twelve accessions were highly resistant to both leaf and stripe rust diseases and also carried the 5HL QTL. We subsequently surveyed the physical region at the 5HL locus for across the barley pan genome variation in the presence of known resistance gene candidates and identified a rich source of high confidence protein kinase and antifungal genes in the QTL region.

Variable exposure to echocardiography core competencies when applying minimum recommended procedural numbers for cardiology fellows in training.

BACKGROUND: The American College of Cardiology Core Cardiovascular Training Statement (COCATS) defined echocardiography core competencies and set the minimum recommend number of echocardiograms to perform (150) and interpret (300) for independent practice in echocardiography (level 2 training). Fellows may lack exposure to key pathologies that are relatively infrequent, however, even when achieving an adequate number of studies performed and interpreted. We hypothesized that cardiology fellows would lack exposure to 1 or more cardiac pathologies related to core competencies in COCATS when performing and interpreting the minimum recommend number of studies for level 2 training. METHODS: We retrospectively reviewed 11,250 reports from consecutive echocardiograms interpreted (7,500) and performed (3,750) by 25 cardiology fellows at a University tertiary referral hospital who graduated between 2015 and 2019. The first 300 echocardiograms interpreted and the first 150 echocardiograms performed by each fellow were included in the analysis. Echocardiography reports were reviewed for cardiac pathologies relating to core competencies defined in COCATS. RESULTS: All 25 fellows lacked exposure to 1 or more cardiac pathologies related to echocardiography core competencies despite meeting COCATS minimum recommended numbers for echocardiograms performed and interpreted. Pathologies for which 1 or more fellows encountered 0 cases despite meeting the minimum recommended numbers for both echocardiograms performed and interpreted included: pericardial constriction (16/25 fellows), aortic dissection (15/25 fellows), pericardial tamponade (4/25 fellows), valvular mass/thrombus (2/25 fellows), prosthetic valve dysfunction (1/25 fellows), and cardiac chamber mass/thrombus (1/25 fellows). CONCLUSIONS: Cardiology fellows who completed the minimum recommend number of echocardiograms performed and interpreted for COCATS level 2 training frequently lacked exposure to cardiac pathologies, even in a University tertiary referral hospital setting. These data suggest that fellowship programs should monitor pathology case counts for each fellow in training, in addition to the minimum recommend number of echocardiograms defined by COCATS, to ensure competency for independent practice in echocardiography.

Continuous NHANES survey data for environmental ambient and occupational hazard identification-feasibility and preliminary findings for osteoporosis and kidney disease.

The Continuous NHANES Survey provides detailed health and environmental chemical burden information on the U.S. population. As of 2012, there were data for 72,000 participants. Based on single biomarker determinations, cumulative burdens were estimated. Because age distributions would differ comparing ambient environmental and occupational exposures, a procedure to distinguish ambient from likely occupational exposures was applied. Associations are reported for osteoporosis and kidney disease-related outcomes with cadmium, lead, and other metals. Cumulative cadmium burden (from blood cadmium, ambient and occupational) was a strong predictor of bone fracture risk and ambient tungsten also had a positive association. Cumulative lead (ambient and occupational) had a negative ("protective") association with fractures as did mercury (occupational). Bone mineral density was statistically significant and similarly predicted by metal exposures. Kidney disease was significantly associated with cumulative lead burdens from both the estimated ambient and occupational sources and with ambient blood cadmium but was most strongly associated with cumulative occupational uranium burden. Systolic blood pressure statistically significantly increased with cumulative ambient and occupational lead (blood) burden and with ambient cadmium and cobalt. Diastolic blood pressure was significantly associated with several cadmium and cobalt metrics along with ambient and occupational cumulative burdens for lead. For environmental substances with burden half-lives measured in years, NHANES offers opportunities for hypothesis generation and confirmation.

TaNAC35 acts as a negative regulator for leaf rust resistance in a compatible interaction between common wheat and Puccinia triticina.

NAC (NAM, AFAT1/2, and CUC2) transcription factors play important roles in plant growth and in resistance to abiotic and biotic stresses. Here, we show that the TaNAC35 gene negatively regulates leaf rust resistance in the wheat line Thatcher + Lr14b (TcLr14b) when challenged with a virulent isolate of Puccinia triticina (Pt). The TaNAC35 gene was cloned from this line, and blastp results showed that its open reading frame (ORF) was 96.16% identical to the NAC35-like sequence reported from Aegilops tauschii, and that it encoded a protein with 387 amino acids (aa) including a conserved NAM domain with 145 aa at the N-terminal alongside the transcriptional activation domain with 220 aa in the C-terminal. Yeast-one-hybrid analysis proved that the C-terminal of the TaNAC35 protein was responsible for transcriptional activation. A 250-bp fragment from the 3'-end of this target gene was introduced to a BSMV-VIGS vector and used to infect the wheat line Thatcher + Lr14b (TcLr14b). The BSMV-VIGS/TaNAC35-infected plant material showed enhanced resistance (infection type "1") to Pt pathotype THTT, which was fully virulent (infection type "4") on BSMV-VIGS only infected TcLr14b plants. Histological studies showed that inhibition of TaNAC35 reduced the formation of haustorial mother cells (HMC) and mycelial growth, implying that the TaNAC35 gene plays a negative role in the response of TcLr14b to Pt pathotype THTT. These results provide molecular insight into the interaction between Pt and its wheat host, and identify a potential target for engineering resistance in wheat to this damaging pathogen.

BED domain-containing NLR from wild barley confers resistance to leaf rust.

Leaf rust, caused by Puccinia hordei, is a devastating fungal disease affecting barley (Hordeum vulgare subsp. vulgare) production globally. Despite the effectiveness of genetic resistance, the deployment of single genes often compromises durability due to the emergence of virulent P. hordei races, prompting the search for new sources of resistance. Here we report on the cloning of Rph15, a resistance gene derived from barley's wild progenitor H. vulgare subsp. spontaneum. We demonstrate using introgression mapping, mutation and complementation that the Rph15 gene from the near-isogenic line (NIL) Bowman + Rph15 (referred to as BW719) encodes a coiled-coil nucleotide-binding leucine-rich repeat (NLR) protein with an integrated Zinc finger BED (ZF-BED) domain. A predicted KASP marker was developed and validated across a collection of Australian cultivars and a series of introgression lines in the Bowman background known to carry the Rph15 resistance. Rph16 from HS-680, another wild barley derived leaf rust resistance gene, was previously mapped to the same genomic region on chromosome 2H and was assumed to be allelic with Rph15 based on genetic studies. Both sequence analysis, race specificity and the identification of a knockout mutant in the HS-680 background suggest that Rph15- and Rph16-mediated resistances are in fact the same and not allelic as previously thought. The cloning of Rph15 now permits efficient gene deployment and the production of resistance gene cassettes for sustained leaf rust control.

Incursions of divergent genotypes, evolution of virulence and host jumps shape a continental clonal population of the stripe rust pathogen Puccinia striiformis.

Long-distance migration and host adaptation by transboundary plant pathogens often brings detrimental effects to important agroecosystems. Efficient surveillance as a basis for responding to the dynamics of such pathogens is often hampered by a lack of information on incursion origin, evolutionary pathways and the genetic basis of rapidly evolving virulence across larger timescales. Here, we studied these genetic features by using historical isolates of the obligate biotrophic pathogen Puccinia striiformis f. sp. tritici (Pst), which causes one of the most widespread and devastating diseases, stripe (yellow) rust, of wheat. Through a combination of genotypic, phenotypic and genomic analyses, we assigned eight Pst isolates representing putative exotic Pst incursions into Australia to four previously defined genetic groups, PstS0, PstS1, PstS10 and PstS13. We showed that isolates of an additional incursion of P. striiformis, known locally as P. striiformis f. sp. pseudo-hordei, had a new and unique multilocus SSR genotype (MLG). We provide results of overall genomic variation of representative Pst isolates from each genetic group by comparative genomic analyses. We showed that isolates within the PstS1 and PstS13 genetic groups are most distinct at the whole-genome variant level from isolates belonging to genetic group PstS0, whereas the isolate from the PstS10 genetic group is intermediate. We further explored variable gene content, including putative effectors, representing both shared but also unique genetic changes that have occurred following introduction, some of which may additionally account for local adaptation of these isolates to triticale. Our genotypic and genomic data revealed new genetic insights into the evolution of diverse phenotypes of rust pathogens following incursion into a geographically isolated continental region.

Adaptive defence and sensing responses of host plant roots to fungal pathogen attack revealed by transcriptome and metabolome analyses.

Plant root-produced constitutive and inducible defences inhibit pathogenic microorganisms within roots and in the rhizosphere. However, regulatory mechanisms underlying host responses during root-pathogen interactions are largely unexplored. Using the model species Brachypodium distachyon (Bd), we studied transcriptional and metabolic responses altered in Bd roots following challenge with Fusarium graminearum (Fg), a fungal pathogen that causes diseases in diverse organs of cereal crops. Shared gene expression patterns were found between Bd roots and spikes during Fg infection associated with the mycotoxin deoxynivalenol (DON). Overexpression of BdMYB78, an up-regulated transcription factor, significantly increased root resistance during Fg infection. We show that Bd roots recognize encroaching Fg prior to physical contact by altering transcription of genes associated with multiple cellular processes such as reactive oxygen species and cell development. These changes coincide with altered levels of secreted host metabolites detected by an untargeted metabolomic approach. The secretion of Bd metabolites was suppressed by Fg as enhanced levels of defence-associated metabolites were found in roots during pre-contact with a Fg mutant defective in host perception and the ability to cause disease. Our results help to understand root defence strategies employed by plants, with potential implications for improving the resistance of cereal crops to soil pathogens.

Resistance in Maize (Zea mays) to Isolates of Puccinia sorghi from Eastern Australia.

The causal agent of maize common rust (CR), Puccinia sorghi, has increased in incidence and severity in Australia in recent years, prompting the assessment of sources of resistance and a preliminary survey of the diversity of P. sorghi populations. The maize commercial hybrids tested carried no resistance to 14 isolates of P. sorghi and had infection types comparable with that of a susceptible check. The resistance gene Rp1_D that remained effective in the United States for 35 years was ineffective against 7 of the 14 isolates. Maize lines carrying known "resistance to Puccinia" (Rp) genes were inoculated with the five isolates considered most diverse based on year of collection (2018 or 2019), location (Queensland or Victoria), and host from which they were isolated (maize or sweet corn). Lines carrying the resistance genes RpG, Rp5, Rp1_E, Rp1_I, Rp1_L, RpGDJ, RpGJF, and Rp5GCJ were resistant to all five isolates and to isolates collected in many agroecological regions. These lines were recommended as donors of effective resistance for maize breeding programs in Australia. Lines carrying no known resistance or resistance genes Rp8_A, Rp8_B, Rp1_J, Rp1_M, Rp7, and Rpp9 (conferring resistance to P. polysora) were susceptible to all five isolates. Differential lines carrying resistance genes Rp1_B, Rp1_C, Rp1_D, Rp1_F, Rp1_K, Rp3_D, or Rp4_A were either resistant or susceptible depending upon the isolate used, showing that the isolates varied in virulence for these genes. Urediniospore production was reduced on adult compared with juvenile plants, presumably due to changes in plant physiology associated with age or the presence of adult plant resistance.

Risk assessment for o-toluidine and bladder cancer incidence.

BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk.

Components of Brachypodium distachyon resistance to nonadapted wheat stripe rust pathogens are simply inherited.

Phytopathogens have a limited range of host plant species that they can successfully parasitise ie. that they are adapted for. Infection of plants by nonadapted pathogens often results in an active resistance response that is relatively poorly characterised because phenotypic variation in this response often does not exist within a plant species, or is too subtle for genetic dissection. In addition, complex polygenic inheritance often underlies these resistance phenotypes and mutagenesis often does not impact upon this resistance, presumably due to genetic or mechanistic redundancy. Here it is demonstrated that phenotypic differences in the resistance response of Brachypodium distachyon to the nonadapted wheat stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst) are genetically tractable and simply inherited. Two dominant loci were identified on B. distachyon chromosome 4 that each reduce attempted Pst colonisation compared with sib and parent lines without these loci. One locus (Yrr1) is effective against diverse Australian Pst isolates and present in two B. distachyon mapping families as a conserved region that was reduced to 5 candidate genes by fine mapping. A second locus, Yrr2, shows Pst race-specificity and encodes a disease resistance gene family typically associated with host plant resistance. These data indicate that some components of resistance to nonadapted pathogens are genetically tractable in some instances and may mechanistically overlap with host plant resistance to avirulent adapted pathogens.

The Coiled-Coil NLR Rph1, Confers Leaf Rust Resistance in Barley Cultivar Sudan.

Unraveling and exploiting mechanisms of disease resistance in cereal crops is currently limited by their large repeat-rich genomes and the lack of genetic recombination or cultivar (cv)-specific sequence information. We cloned the first leaf rust resistance gene Rph1 (Rph1 a) from cultivated barley (Hordeum vulgare) using "MutChromSeq," a recently developed molecular genomics tool for the rapid cloning of genes in plants. Marker-trait association in the CI 9214/Stirling doubled haploid population mapped Rph1 to the short arm of chromosome 2H in a physical region of 1.3 megabases relative to the barley cv Morex reference assembly. A sodium azide mutant population in cv Sudan was generated and 10 mutants were confirmed by progeny-testing. Flow-sorted 2H chromosomes from Sudan (wild type) and six of the mutants were sequenced and compared to identify candidate genes for the Rph1 locus. MutChromSeq identified a single gene candidate encoding a coiled-coil nucleotide binding site Leucine-rich repeat (NLR) receptor protein that was altered in three different mutants. Further Sanger sequencing confirmed all three mutations and identified an additional two independent mutations within the same candidate gene. Phylogenetic analysis determined that Rph1 clustered separately from all previously cloned NLRs from the Triticeae and displayed highest sequence similarity (89%) with a homolog of the Arabidopsis (Arabidopsis thaliana) disease resistance protein 1 protein in Triticum urartu In this study we determined the molecular basis for Rph1-mediated resistance in cultivated barley enabling varietal improvement through diagnostic marker design, gene editing, and gene stacking technologies.

Molecular genetics of leaf rust resistance in wheat and barley.

The demand for cereal grains as a main source of energy continues to increase due to the rapid increase in world population. The leaf rust diseases of cereals cause significant yield losses, posing challenges for global food security. The deployment of resistance genes has long been considered as the most effective and sustainable way to control cereal leaf rust diseases. While genetic resistance has reduced the impact of these diseases in agriculture, losses still occur due to the ability of the respective rust pathogens to change and render resistance genes ineffective plus the slow pace at which resistance genes are discovered and characterized. This article highlights novel recently developed strategies based on advances in genome sequencing that have accelerated gene isolation by overcoming the complexity of cereal genomes. The leaf rust resistance genes cloned so far from wheat and barley belong to various protein families, including nucleotide binding site/leucine-rich repeat receptors and transporters. We review recent studies that are beginning to reveal the defense mechanisms conferred by the leaf rust resistance genes identified to date in cereals and their roles in either pattern-triggered immunity or effector-triggered immunity.

Fine mapping of leaf rust resistance gene Rph13 from wild barley.

KEY MESSAGE: Fine mapping of the barley leaf rust resistance locus Rph13 on chromosome 3HL facilitates its use in breeding programs through marker-assisted selection. Barley leaf rust (BLR-caused by Puccinia hordei) is a widespread fungal disease that can be effectively controlled by genetic resistance. There is an ongoing need to both diversify and genetically characterise resistance loci to provide effective and durable control given the ongoing threat of rapidly evolving P. hordei populations. Here, we report on the molecular genetic characterisation of the Rph13 locus, originally derived from wild barley and transferred to barley accession Berac (then referred to as PI 531849). The 2017 reference genome of cv. Morex was used as a road map to rapidly narrow both a genetic and physical intervals around the Rph13 resistance locus. Using recombination-based mapping, we narrowed the physical interval to 116.6 kb on chromosome 3H in a segregating population of a cross of the Rph13 carrying resistant line PI 531849 with the leaf rust-susceptible cultivar Gus. We identified two nucleotide-binding leucine-rich repeat genes as likely candidates for the Rph13 resistance. Sequences from the candidate genes enabled the development of a KASP marker that distinguished resistant and susceptible progeny and was found to be predictive and useful for MAS.

Inheritance and Characterization of Rph27: A Third Race-Specific Resistance Gene in the Barley Cultivar Quinn.

The barley cultivar Quinn was previously reported to carry two genes for resistance to Puccinia hordei, viz. Rph2 and Rph5. In this study, we characterized and mapped a third resistance gene (RphCRQ3) in cultivar Quinn. Multipathotype testing in the greenhouse on a panel of barley genotypes previously postulated to carry Rph2 revealed rare race specificity in four genotypes in response to P. hordei pathotype (pt.) 222 P+ (virulent on Rph2 and Rph5). This suggested either the presence of a race-specific allele variant of Rph2 or the presence of an independent uncharacterized leaf rust resistance locus. A test of allelism on 1,271 F2 Peruvian (Rph2)/Quinn (Rph2 + Rph5) derived seedlings with P. hordei pt. 220 P+ (avirulent on Rph2 and virulent on Rph5) revealed no susceptible segregants. To determine whether the race-specific resistance in Quinn was due to an allele of Rph2 on chromosome 5H or a third uncharacterized resistance gene, we tested the Peruvian/Quinn F3 population with 222 P+ and observed monogenic inheritance. Subsequent bulked segregant analysis indicated the presence of complete in-phase marker fixation near the telomere on the short arm of chromosome 4H, confirming the presence of a third resistance locus in Quinn in addition to Rph2 and Rph5. In accordance with the rules and numbering system of barley gene nomenclature, RphCRQ3 has been designated Rph27.

Associations between exposure to ethylene oxide, job termination, and cause-specific mortality risk.

BACKGROUND: Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed. METHODS: To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes. RESULTS: Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds. CONCLUSIONS: Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.

A Simple Toxicokinetic Model Exhibiting Complex Dynamics and Nonlinear Exposure Response.

Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects.