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Prospective outcomes of adults with speciated Mycobacterium avium complex lung disease, 2021-2026.

RATIONALE: Mycobacterium avium complex lung disease (MAC-LD) is clinically heterogeneous and carries diverse outcomes. OBJECTIVES: To describe predictors of clinical progression of MAC-LD in a state-wide cohort. METHODS: We enrolled adults with MAC-LD from across Virginia, USA starting in 2021. Every 6 months we performed respiratory quality of life questionnaire, scored CT scans, and recorded respiratory mycobacterial cultures including MAC speciation. Outcomes were classified using NTM-NET consensus definitions, factors predicting clinical progression analyzed by Poisson regression, and hierarchical clustering on principal components derived from Factorial Analysis of Mixed Data. MEASUREMENTS AND MAIN RESULTS: Of 105 participants the median follow-up was 917 days. Mean age was 69.8 years, 79 (75%) were women, and 70 (67%) had nodular bronchiectasis. M. intracellulare was the most common species, present in 48 (46%) participants at enrollment, followed by M. avium (29, 28%), and M. intracellulare subspecies chimaera (11, 10%). Only 2 (9%) of 22 evaluable participants met the NTM-NET definition of cure. In all participants after multivariable adjustment, older baseline age (incidence rate ratio 1.03 [1, 1.06], p = 0.04) and fibrocavitary CT scan pattern (2.57 [1.33, 4.96], p = 0.005), were associated with unfavorable 12-month clinical progression. Species type and species persistence contributed to characteristics of three distinct phenotypes of MAC-LD of varying severity and clinical progression. CONCLUSIONS: The majority of participants were not assessable for MAC-LD treatment outcomes using strict NTM-NET definitions. Species informed phenotypes of MAC lung disease are prognostically useful and can inform routine management and trial design.

M. intracellulare↗

Expert judgment and occupational hygiene: application to aerosol speciation in the nickel primary production industry.

In many situations characterized by sparse data, occupational hygienists have used subjective judgments that are claimed to be derived from their experience and knowledge. While this practice is widespread, there has been no systematic study of 'expert judgment' or the 'art' of occupational hygiene. Indeed, there is a need to address the question of whether there is such a thing as 'expert opinion' in occupational hygiene that is broadly shared by practicing professionals. This research, employing 11 experts who estimate an exposure parameter (the percentages of four nickel species) in 12 workplaces in a nickel primary production industry, provides a large dataset from which useful inferences can be drawn about the quality of expert judgments and the variability among the experts. A well-designed questionnaire that provided succinct information about the processes and baseline data served to calibrate the experts. The Bayesian framework has been used in this work to develop posterior means and standard deviations of the percentages of the four nickel species in the 12 workplaces of interest in the company. These estimates of the nickel speciation are at least as precise as--and most of the time more precise than--those provided by the sparse measurement data. There was a very high degree of agreement among the experts. A majority of the experts agreed among themselves 92% of the time, while almost two-thirds agreed 73% of the time. This, coupled with the fact that the experts came from varied backgrounds, seems to suggest that there is indeed some broad body of specialized knowledge that the experts are drawing on to reach similar judgments. It also seems that one type of expert is not necessarily any better than any other kind, and expertise does not necessarily require intimate familiarity with the workplace. In this example, the expert judgment exercise has indeed enhanced the quality of our knowledge of the exposure 'fingerprints' for the nickel industry workplaces studied and the combination of expert judgment and sparse data is better than the sparse data alone. For occupational hygiene exposure assessment, our experience suggests that such expert judgment methods can provide a cost-effective means to improve and refine information about workplace hazards. However, more study is warranted for situations where the domain of the quantity of interest has a much wider range of values, e.g. actual exposure values.

Air Pollutants, Occupational↗

Size distribution and speciation of chromium in paint spray aerosol at an aerospace facility.

Spray painters are potentially exposed to aerosol containing Cr(VI) via inhalation of chromate-based paint spray. Two field studies were conducted at an aerospace facility to determine the size distribution and speciation of Cr(VI) in paint spray aerosol. Sampled paint products consisted of sparingly soluble strontium chromate in an epoxy resin matrix, a matrix generally known for its durability and toughness. Personal aerosol samples were collected using Sierra Marple personal cascade impactors and analyzed for Cr(VI) and total Cr. The size distribution of total Cr particles in the paint aerosol had a Mass Median Aerodynamic Diameter (MMAD) of 7.5 mum [Geometric Standard Deviation (GSD = 2.7 mum)] in both field studies. The MMAD of Cr(VI) particles was 8.5 mum (GSD = 2.2 mum). Particles >2 mum constituted 90% or more of the total Cr and the Cr(VI) mass, in all sampled paint aerosols and were lognormally distributed. The target site for respiratory deposition of Cr in the aerosol was estimated based on the mass distribution of Cr according to particle size. On an average, 62% of the Cr and Cr(VI) mass in the paint aerosol consisted of particles >10 mum. This study showed that 71.8% of Cr(VI) mass in paint spray aerosol potentially inhaled by a spray painter may deposit in the head airways region. Only 2.0 and 1.4% of Cr(VI) mass in the paint aerosol may potentially deposit in the alveolar and tracheobronchial region, respectively. The ratio of Cr(VI) mass to total Cr mass was determined in bulk paint and the data indicate that Cr was predominantly in the Cr(VI) valence state, before spraying. The ratio of Cr(VI) mass to total Cr mass was also determined in paint aerosol samples. The data indicated that there was a reduction of Cr(VI) regardless of Cr aerosol particle size. Cr(VI) reduction occurred most likely during the 8 h sample collection time period. These findings are in agreement with the findings that observed Cr(VI) reduction during collection of airborne Cr(VI) in samples of chromic acid mist. The use of Cr(VI) stabilizing sampling media and the storage of samples at lower temperatures (4 degrees C ) during and after sampling may avoid the underestimation of Cr(VI).

Aerosols↗

Evaluation of copper speciation and water quality factors that affect aqueous copper tasting response.

This study determined taste thresholds for copper as its speciation was varied among free cupric ion, complexed cupric ion, and precipitated cupric particles. The impact of copper chemistry on taste is important as copper is added to many beverages and can be present in drinking water as a natural mineral or due to corrosion of copper plumbing. A one-of-five test was used to define thresholds with solutions containing 0.025-8 mg/l Cu (from copper sulfate) in distilled or mineralized water of varying pH. The mineralized water was designed to mimic the composition of a typical tap water. Group thresholds for copper in either distilled-deionized water or mineralized water were not significantly different and ranged from 0.4 to 0.8 mg/l Cu. A difference from control test was used to assess the impact of soluble and particulate copper on taste. Soluble copper species, including free cupric ion and complexed copper species, were readily tasted, while particulate copper was poorly tasted.

Adult↗

Lead speciation by HPLC-ICP-AES and HPLC-ICP-MS.

Speciation of inorganic lead (Pb2+) and several trialkyllead species (trimethyllead chloride [TML], triethyllead chloride [TEL], and triphenyllead chloride [TPhL]) is investigated using high-performance liquid chromatography (HPLC) with detection by both inductively coupled plasma emission spectroscopy (ICP-AES), and inductively coupled plasma mass spectrometry (ICP-MS). Reversed-phase, ion-pairing, and ion-exchange HPLC modes are studied. Optimal chromatographic conditions for ICP-AES detection include a reversed-phase separation utilizing a step gradient from 10 to 70% methanol. However, the gradient has been found to destabilize the plasma when using ICP-MS detection. An isocratic separation with a 30% methanol mobile phase has been found to be the best compromise between plasma stability and chromatographic resolution. Detection limits using ICP-MS detection are 3 orders of magnitude improved over ICP-AES detection.

Chromatography, High Pressure Liquid↗

Determination of total and speciated sulfur content in petrochemical samples using a pulsed flame photometric detector.

The pulsed flame photometric detector (PFPD) has the advantage of being able to measure the concentration of individual sulfur compounds and total sulfur content in a petrochemical sample in a single gas chromatography run. Because it is an equimolar response detector, the PFPD's sulfur response is independent of a compound's molecular structure, and this feature allows quantitation of the total or speciated sulfur content in complex samples using a single calibrant. This paper is a survey describing a variety of applications using the PFPD for sulfur quantitation in petrochemical matrices. Several different approaches to quantitation are described, and simple techniques for circumventing the quenching of the sulfur signal by coeluting hydrocarbon peaks are discussed. Examples from a range of real-world samples are presented.

Journal Article↗

Rapid speciation analysis of Cr(VI) and Cr(III) by reversed-phase high-performance liquid chromatography with UV detection.

A simple and rapid method is developed for the simultaneous determination of Cr(VI) and Cr(III) based on the formation of their different complexes with ammonium pyrrolidine-dithiocarbamate (APDC). Separation is performed using reversed-phase high-performance liquid chromatography coupled with UV detection. The conditions for complex formation and speciation are determined, such as solution pH, amount of APDC, temperature, and type of mobile phase. In order to substantially reduce the analysis time, the separation is carried out without extraction of chromium-APDC complexes from the mother liquor. Under the optimum analysis conditions, the chromatograms obtained show good peak separation, and the absolute detection limits (3s) are 2.2 microg/L for Cr(VI) and 4.5 microg/L for Cr(III). The calibration curves are linear from 3 to 5000 microg/L for Cr(VI) and 5 to 3000 microg/L for Cr(III). The relative standard deviations of peak areas in five measurements using a sample solution of 200 microg/L are less than 2% for Cr(VI) and 4% for Cr(III), indicating good reproducibility for this analytical method. Furthermore, simultaneous determination of Cr(VI) and Cr(III) is successful with the application of the proposed procedure in the synthetic wastewaters containing common heavy metal ions: Fe(III), Pb(II), Cd(II), Cu(II), and Zn(II).

Journal Article↗

Speciation by reinforcement: a model derived from studies of Drosophila.

Reinforcement is an increase in premating reproductive isolation between taxa resulting from selection against hybrids. We present a model of reinforcement with a novel type of selection on female mating behavior. Previous models of reinforcement have focused on the divergence of female mating preferences between nascent species. We suggest that an increase in the level of female mating discrimination can yield reinforcement without further divergence of either male characters or female preferences. This model indicates that selection on mating discrimination is a viable mechanism for reinforcement and may allow speciation under less stringent conditions than selection on female preference. This model also incorporates empirical results from genetic studies of hybrid fitness determination in Drosophila species. We find that the details of inheritance, which include sex-linked transmission, sex-limited fertility reduction, and X-autosome epistasis, have important effects on the likelihood of reinforcement. In particular, X-autosome epistasis for hybrid fitness determination facilitates reinforcement when hybrid fertility reduction occurs in males, but hinders the process when it occurs in females. HALDANE's rule indicates that hybrid sterility will generally evolve in males prior to females within nascent species. Thus, HALDANE's rule and X-autosome epistasis provide conditions that are surprisingly favorable for reinforcement in Drosophila.

Animals↗

Incipient speciation by sexual isolation in Drosophila melanogaster: extensive genetic divergence without reinforcement.

The collection of Drosophila melanogaster from Zimbabwe and nearby regions (the Z-type) yield females who would not mate with the cosmopolitan D. melanogaster males (the M-type). To dissect the genetic basis of this sexual isolation, we constructed 16 whole-chromosome substitution lines between two standard Z- and M-lines. The results were as follows: (1) All substitution lines appear normal in viability and fertility in both sexes, indicating no strong postmating isolation. (2) The genes for the behaviors are mapped to all three major chromosomes with the same ranking and comparable magnitude of effects for both sexes: III > II >> X > or = 0 (III, II and X designate the effects of the three chromosomes). The results suggest less evolution on the X than on autosomes at loci of sexual behavior. (3) The genes for "Z-maleness" are many and somewhat redundant. Whole-chromosome effects for Z-maleness appear nearly additive and show little dominance. (4) In contrast, "Z-femaleness" has less redundancy as partial genotypes never exhibit full phenotypic effects. Epistatic interactions and incomplete dominance can sometimes be detected. (5) The extensive genetic divergence underlying sexual isolation has evolved in the absence of detectable reduction in hybrid fitnesses. Sexual selection has apparently been a driving force of multiple facets of speciation at the nascent stage without reinforcement.

Animals↗

Speciation and domestication in maize and its wild relatives: evidence from the globulin-1 gene.

The grass genus Zea contains the domesticate maize and several wild taxa indigenous to Central and South America. Here we study the genetic consequences of speciation and domestication in this group by sampling DNA sequences from four taxa-maize (Zea mays ssp. mays), its wild progenitor (Z. mays ssp. parviglumis), a more distant species within the genus (Z. luxurians), and a representative of the sister genus (Tripsacum dactyloides). We sampled a total of 26 sequences from the glb1 locus, which encodes a nonessential seed storage protein. Within the Zea taxa sampled, the progenitor to maize contains the most sequence diversity. Maize contains 60% of the level of genetic diversity of its progenitor, and Z. luxurians contains even less diversity (32% of the level of diversity of Z. mays ssp. parviglumis). Sequence variation within the glb1 locus is consistent with neutral evolution in all four taxa. The glb1 data were combined with adh1 data from a previous study to make inferences about the population genetic histories of these taxa. Comparisons of sequence data between the two morphologically similar wild Zea taxa indicate that the species diverged approximately 700, 000 years ago from a common ancestor of intermediate size to their present populations. Conversely, the domestication of maize was a recent event that could have been based on a very small number of founding individuals. Maize retained a substantial proportion of the genetic variation of its progenitor through this founder event, but diverged rapidly in morphology.

Alcohol Dehydrogenase↗

Genetic composition and diploid hybrid speciation of a high mountain pine, Pinus densata, native to the Tibetan plateau.

Pinus densata has been suggested to have originated from hybridization events involving P. tabulaeformis and P. yunnanensis. In this study, allozyme differentiation at 12 loci was studied in 14 populations of P. tabulaeformis, P. densata, and P. yunnanensis from China. The observed genetic composition of P. densata supported the hybrid hypothesis and showed varying degrees of contribution from P. yunnanensis and P. tabulaeformis among its populations. These data, together with previous chloroplast DNA results, indicated different evolutionary histories among P. densata populations. To examine the possibility of ongoing hybridization among the three species, we analyzed patterns of linkage disequilibria between allozyme loci in ovule, pollen, and zygote pools. None of these tests suggested that there is significant ongoing gene exchange, implying that populations of P. densata have a stabilized hybrid nature. The normal fertility and high fecundity of P. densata indicate that this hybrid is maintained through sexual reproduction. P. densata represents an example of diploid hybrid speciation in an extreme ecological habitat that is both spatially and ecologically separated from that of its parents.

Alleles↗

Inactivation of E alpha and E beta expression in inbred and wild mice by multiple distinct mutations, some of which predate speciation within Mus species.

The H-2 MHC of mice encodes two functional class II heterodimeric proteins: A alpha A beta (A) and E alpha E beta (E). While failure to express the A protein has not been reported, a significant proportion of of H-2 haplotypes in both inbred and wild mice do not express E proteins. We and others have previously characterized the molecular basis for defective E expression in haplotypes from Mus domesticus (b, f, q, s, from inbred strains) and M. castaneus (w17, wild-derived) species, identifying six distinct defects in the genes for E alpha or E beta. In this report we have extended these studies to other E- haplotypes, including several from t-haplotype-bearing M. domesticus mice (w29, w57, w302) and one derived from the Asian species M. bactrianus (w301). Analyses at the protein, RNA and DNA levels were employed to identify the defects in the genes for Ea and Eb. At least one new defect was identified that prevents E beta expression in a t-associated H-2 haplotypes (w57), bringing the number of distinct mutations causing the E- phenotype to seven. Another t-associated haplotype, w302, was found to share the same E beta defect with mice of the inbred q haplotype and of the w17 haplotype from M. castaneus, while its Ea gene contains the deletion carried also by the inbred b and s haplotypes and by a number of wild haplotypes. The mutations in the Ea and Eb genes of the w301 haplotype from M. bactrianus were found to be identical to those of the inbred f haplotype. This indicates that the origin of the mutations in the Eb genes of the q, w17 and w302 haplotypes and in the Ea and Eb genes of the f and w301 haplotypes, predated speciation within Mus, thought to have occurred approximately 0.35-1 million years ago. Their maintenance in mouse populations suggests that in certain conditions the failure to express E alpha E beta proteins may be advantageous and selected for.

Amino Acid Sequence↗

Speciation of arsenic compounds in urine from occupationally unexposed and exposed persons in the U.K. using a routine LC-ICP-MS method.

This paper describes a routine, robust, and reproducible liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) speciation method for five arsenic compounds [arsenobetaine (AB), arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)] in urine. Concentrations of these arsenic species in urine samples are reported in two sets of non-occupationally exposed controls with one set having consumed fish within 24 h (n = 31) and the other not having consumed fish for 48 h (n = 34). Arsenic species in urine samples from workers in both the timber treatment industry (n = 49) and semiconductor industry (n = 46) are also reported. The arsenic content in all of the samples was also determined using hydride-generation coupled with ICP-MS. The results show that urine samples from people not occupationally exposed to arsenic contain low levels of DMA, MMA, and AB and that only urine from smokers contained any inorganic arsenic. Consumption of seafood was seen to significantly increase the levels of AB and DMA in the unexposed persons. Urine samples from the semiconductor workers exhibited significantly higher levels of arsenite, arsenate, and DMA than the unexposed samples. The urine samples from timber treatment workers exhibited significantly higher levels of four arsenic species (not AB) than those observed in both the control groups and the semi-conductor workers.

Anion Exchange Resins↗

Significantly different patterns of amino acid replacement after gene duplication as compared to after speciation.

We have performed a large-scale analysis of amino acid sequence evolution after gene duplication by comparing evolution after gene duplication with evolution after speciation in over 1,800 phylogenetic trees constructed from manually curated alignments of protein domains downloaded from the PFAM database. The site-specific rate of evolution is significantly altered by gene duplication. A significant increase in the proportion of amino acid substitutions at constrained (slowly evolving) sites after duplication was observed. An increase in the proportion of replacements at normally constrained amino acid sites could result from relaxation of purifying selective pressure. However, the proportion of amino acid replacements involving radical changes in amino acid properties after duplication does not appear to be significantly increased by relaxed selective pressure. The increased proportion of replacements at constrained sites was observed over a relatively large range of protein change (up to 25% amino acid replacements per site). These findings have implications for our understanding of the nature of evolution after duplication and may help to shed light on the evolution of novel protein functions through gene duplication.

Algorithms↗

Origin and speciation of haplochromine fishes in East African crater lakes investigated by the analysis of their mtDNA, Mhc genes, and SINEs.

The Western Branch of the East African Great Rift Valley is pocketed with craters of extinct or dormant volcanoes. Many of the craters are filled with water, and the lakes are inhabited by fishes. The objective of the present study was to determine the amount and nature of genetic variation in haplochromine fishes inhabiting two of these crater lakes, Lake Lutoto and Lake Nshere, and to use this information to infer the origin and history of the two populations. To this end, sequences of mitochondrial (mt) DNA control region, exon 2 of major histocompatibility complex (Mhc) class II B genes, and short interspersed elements (SINEs) were analyzed. The results indicate that the Lake Nshere and Lake Lutoto fishes originated from different but related large founding populations derived from the Kazinga Channel, which connects Lake Edward and Lake George. Some of the genetic polymorphism that existed in the ancestral populations was lost in the populations of the two lakes. The polymorphism that has been retained has persisted for some 50000 generations (years). During this time, new mutations arose and became fixed in each of the two populations in the mtDNA, giving rise to sets of diagnostic substitutions. Each population evolved in isolation after the colonization of the lakes less than 50000 years ago. There appears to be no population structure within the crater lake fishes, and their present effective population sizes are in the order of 104 to 105 individuals. Comparisons with the endemic haplochromine species of Lake Victoria reveal interesting parallels, as well as differences, which may help to understand the nature of the speciation process.

Africa, Eastern↗

Speciation and intrasubspecific variation of Bornean orangutans, Pongo pygmaeus pygmaeus.

Mitochondrial DNA control region sequences of orangutans (Pongo pygmaeus) from six different populations on the island of Borneo were determined and analyzed for evidence of regional diversity and were compared separately with orangutans from the island of Sumatra. Within the Bornean population, four distinct subpopulations were identified. Furthermore, the results of this study revealed marked divergence, supportive evidence of speciation between Sumatran and Bornean orangutans. This study demonstrates that, as an entire population, Bornean orangutans have not experienced a serious genetic bottleneck, which has been suggested as the cause of low diversity in humans and east African chimpanzees. Based on these new data, it is estimated that Bornean and Sumatran orangutans diverged approximately 1.1 MYA and that the four distinct Bornean populations diverged 860,000 years ago. These findings have important implications for management, breeding, and reintroduction practices in orangutan conservation efforts.

Animals↗

Inferring the history of speciation from multilocus DNA sequence data: the case of Drosophila pseudoobscura and close relatives.

The divergence of Drosophila pseudoobscura from its close relatives, D. persimilis and D. pseudoobscura bogotana, was examined using the pattern of DNA sequence variation in a common set of 50 inbred lines at 11 loci from diverse locations in the genome. Drosophila pseudoobscura and D. persimilis show a marked excess of low-frequency variation across loci, consistent with a model of recent population expansion in both species. The different loci vary considerably, both in polymorphism levels and in the levels of polymorphisms that are shared by different species pairs. A major question we address is whether these patterns of shared variation are best explained by gene flow or by persistence since common ancestry. A new test of gene flow, based on patterns of linkage disequilibrium, is developed. The results from these, and other tests, support a model in which D. pseudoobscura and D. persimilis have exchanged genes at some loci. However, the pattern of variation suggests that most gene flow, although occurring after speciation began, was not recent. There is less evidence of gene flow between D. pseudoobscura and D. p. bogotana. The results are compared with recent work on the genomic locations of genes that contribute to reproductive isolation between D. pseudoobscura and D. persimilis. We show that there is a good correspondence between the genomic regions associated with reproductive isolation and the regions that show little or no evidence of gene flow.

Animals↗

The plastid chromosome of Atropa belladonna and its comparison with that of Nicotiana tabacum: the role of RNA editing in generating divergence in the process of plant speciation.

The nuclear and plastid genomes of the plant cell form a coevolving unit which in interspecific combinations can lead to genetic incompatibility of compartments even between closely related taxa. This phenomenon has been observed for instance in Atropa-Nicotiana cybrids. We have sequenced the plastid chromosome of Atropa belladonna (deadly nightshade), a circular DNA molecule of 156,688 bp, and compared it with the corresponding published sequence of its relative Nicotiana tabacum (tobacco) to understand how divergence at the level of this genome can contribute to nuclear-plastid incompatibilities and to speciation. It appears that (1) regulatory elements, i.e., promoters as well as translational and replicational signal elements, are well conserved between the two species; (2) genes--including introns--are even more highly conserved, with differences residing predominantly in regions of low functional importance; and (3) RNA editotypes differ between the two species, which makes this process an intriguing candidate for causing rapid reproductive isolation of populations.

Amino Acid Sequence↗