Phylogenetic relationships of eight new Dacrymycetes collected from New Zealand.

Dacrymycetes, sister to Agaricomycetes, is a noteworthy lineage for studying the evolution of wood-decaying basidiomycetes; however, its species diversity and phylogeny are largely unknown. Species of Dacrymycetes previously used in molecular phylogenetic analyses are mainly derived from the Northern Hemisphere, thus insufficient knowledge exists concerning the Southern Hemisphere lineages. In this study, we investigated the species diversity of Dacrymycetes in New Zealand. We found 11 previously described species, and eight new species which were described here: Calocera pedicellata, Dacrymyces longistipitatus, D. pachysporus, D. stenosporus, D. parastenosporus, D. cylindricus, D. citrinus, and D. cyrtosporus. These eight newly described species and seven of the known ones, namely, Calocera fusca, C. cf. guepinioides, C. lutea, Dacrymyces flabelliformis, D. intermedius, D. subantarcticensis, and Heterotextus miltinus, have rarely or never been recorded from the Northern Hemisphere. In a molecular-based phylogeny, these New Zealand strains were scattered throughout the Dacrymycetaceae clade. Sequences obtained from specimens morphologically matching C. guepinioides were separated into three distant clades. Because no obvious morphological differences could be discerned between the specimens in each clade and no sequence exists from the type specimen, a C. guepinioides s.str. clade could not be determined. This survey of dacrymycetous species in the Southern Hemisphere has increased taxon sampling for phylogenetic analyses that can serve as a basis for the construction of a stable classification of Dacrymycetes.

Fungal Planet description sheets: 558-624.

Novel species of fungi described in this study include those from various countries as follows: Australia: Banksiophoma australiensis (incl. Banksiophoma gen. nov.) on Banksia coccinea, Davidiellomycesaustraliensis (incl. Davidiellomyces gen. nov.) on Cyperaceae, Didymocyrtis banksiae on Banksia sessilis var. cygnorum, Disculoides calophyllae on Corymbia calophylla, Harknessia banksiae on Banksia sessilis, Harknessia banksiae-repens on Banksia repens, Harknessia banksiigena on Banksia sessilis var. cygnorum, Harknessia communis on Podocarpus sp., Harknessia platyphyllae on Eucalyptus platyphylla, Myrtacremonium eucalypti (incl. Myrtacremonium gen. nov.) on Eucalyptus globulus, Myrtapenidiella balenae on Eucalyptus sp., Myrtapenidiella eucalyptigena on Eucalyptus sp., Myrtapenidiella pleurocarpae on Eucalyptuspleurocarpa, Paraconiothyrium hakeae on Hakea sp., Paraphaeosphaeria xanthorrhoeae on Xanthorrhoea sp., Parateratosphaeria stirlingiae on Stirlingia sp., Perthomyces podocarpi (incl. Perthomyces gen. nov.) on Podocarpus sp., Readeriella ellipsoidea on Eucalyptus sp., Rosellinia australiensis on Banksia grandis, Tiarosporella corymbiae on Corymbia calophylla, Verrucoconiothyriumeucalyptigenum on Eucalyptus sp., Zasmidium commune on Xanthorrhoea sp., and Zasmidium podocarpi on Podocarpus sp. Brazil: Cyathus aurantogriseocarpus on decaying wood, Perenniporia brasiliensis on decayed wood, Perenniporia paraguyanensis on decayed wood, and Pseudocercospora leandrae-fragilis on Leandrafragilis.Chile: Phialocephala cladophialophoroides on human toe nail. Costa Rica: Psathyrella striatoannulata from soil. Czech Republic: Myotisia cremea (incl. Myotisia gen. nov.) on bat droppings. Ecuador: Humidicutis dictiocephala from soil, Hygrocybe macrosiparia from soil, Hygrocybe sangayensis from soil, and Polycephalomyces onorei on stem of Etlingera sp. France: Westerdykella centenaria from soil. Hungary: Tuber magentipunctatum from soil. India: Ganoderma mizoramense on decaying wood, Hodophilus indicus from soil, Keratinophyton turgidum in soil, and Russula arunii on Pterigota alata.Italy: Rhodocybe matesina from soil. Malaysia: Apoharknessia eucalyptorum, Harknessia malayensis, Harknessia pellitae, and Peyronellaea eucalypti on Eucalyptus pellita, Lectera capsici on Capsicum annuum, and Wallrothiella gmelinae on Gmelina arborea.Morocco: Neocordana musigena on Musa sp. New Zealand: Candida rongomai-pounamu on agaric mushroom surface, Candida vespimorsuum on cup fungus surface, Cylindrocladiella vitis on Vitis vinifera, Foliocryphia eucalyptorum on Eucalyptus sp., Ramularia vacciniicola on Vaccinium sp., and Rhodotorula ngohengohe on bird feather surface. Poland: Tolypocladium fumosum on a caterpillar case of unidentified Lepidoptera.Russia: Pholiotina longistipitata among moss. Spain: Coprinopsis pseudomarcescibilis from soil, Eremiomyces innocentii from soil, Gyroporus pseudocyanescens in humus, Inocybe parvicystis in humus, and Penicillium parvofructum from soil. Unknown origin: Paraphoma rhaphiolepidis on Rhaphiolepsis indica.USA: Acidiella americana from wall of a cooling tower, Neodactylaria obpyriformis (incl. Neodactylaria gen. nov.) from human bronchoalveolar lavage, and Saksenaea loutrophoriformis from human eye. Vietnam: Phytophthora mekongensis from Citrus grandis, and Phytophthora prodigiosa from Citrus grandis. Morphological and culture characteristics along with DNA barcodes are provided.

Testing for Hardy-Weinberg equilibrium at biallelic genetic markers on the X chromosome.

Testing genetic markers for Hardy-Weinberg equilibrium (HWE) is an important tool for detecting genotyping errors in large-scale genotyping studies. For markers at the X chromosome, typically the χ(2) or exact test is applied to the females only, and the hemizygous males are considered to be uninformative. In this paper we show that the males are relevant, because a difference in allele frequency between males and females may indicate HWE not to hold. The testing of markers on the X chromosome has received little attention, and in this paper we lay down the foundation for testing biallelic X-chromosomal markers for HWE. We develop four frequentist statistical test procedures for X-linked markers that take both males and females into account: the χ(2) test, likelihood ratio test, exact test and permutation test. Exact tests that include males are shown to have a better Type I error rate. Empirical data from the GENEVA project on venous thromboembolism is used to illustrate the proposed tests. Results obtained with the new tests differ substantially from tests that are based on female genotype counts only. The new tests detect differences in allele frequencies and seem able to uncover additional genotyping error that would have gone unnoticed in HWE tests based on females only.

Unravelling Colletotrichum species associated with Camellia: employing ApMat and GS loci to resolve species in the C. gloeosporioides complex.

We investigated the phylogenetic diversity of 144 Colletotrichum isolates associated with symptomatic and asymptomatic tissues of Camellia sinensis and other Camellia spp. from seven provinces in China (Fujian, Guizhou, Henan, Jiangxi, Sichuan, Yunnan, Zhejiang), and seven isolates obtained from other countries, including Indonesia, UK, and the USA. Based on multi-locus (ACT, ApMat, CAL, GAPDH, GS, ITS, TUB2) phylogenetic analyses and phenotypic characters, 11 species were distinguished, including nine well-characterised species (C. alienum, C. boninense, C. camelliae, C. cliviae, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. sia-mense), and two novel species (C. henanense and C. jiangxiense). Of these, C. camelliae proved to be the most dominant and probably host specific taxon occurring on Camellia. An epitype is also designated for the latter species in this study. Colletotrichum jiangxiense is shown to be phylogenetically closely related to the coffee berry pathogen C. kahawae subsp. kahawae. Pathogenicity tests and the pairwise homoplasy index test suggest that C. jiangxiense and C. kahawae subsp. kahawae are two independent species. This study represents the first report of C. alienum and C. cliviae occurring on Camellia sinensis. In addition, our study demonstrated that the combined use of the loci ApMat and GS in a phylogenetic analysis is able to resolve all currently accepted species in the C. gloeosporioides species complex.

HIBAG--HLA genotype imputation with attribute bagging.

Genotyping of classical human leukocyte antigen (HLA) alleles is an essential tool in the analysis of diseases and adverse drug reactions with associations mapping to the major histocompatibility complex (MHC). However, deriving high-resolution HLA types subsequent to whole-genome single-nucleotide polymorphism (SNP) typing or sequencing is often cost prohibitive for large samples. An alternative approach takes advantage of the extended haplotype structure within the MHC to predict HLA alleles using dense SNP genotypes, such as those available from genome-wide SNP panels. Current methods for HLA imputation are difficult to apply or may require the user to have access to large training data sets with SNP and HLA types. We propose HIBAG, HLA Imputation using attribute BAGging, that makes predictions by averaging HLA-type posterior probabilities over an ensemble of classifiers built on bootstrap samples. We assess the performance of HIBAG using our study data (n=2668 subjects of European ancestry) as a training set and HLA data from the British 1958 birth cohort study (n≈1000 subjects) as independent validation samples. Prediction accuracies for HLA-A, B, C, DRB1 and DQB1 range from 92.2% to 98.1% using a set of SNP markers common to the Illumina 1M Duo, OmniQuad, OmniExpress, 660K and 550K platforms. HIBAG performed well compared with the other two leading methods, HLA*IMP and BEAGLE. This method is implemented in a freely available HIBAG R package that includes pre-fit classifiers for European, Asian, Hispanic and African ancestries, providing a readily available imputation approach without the need to have access to large training data sets.

Aboriginal and Torres Strait Islander youth suicide mortality and previous mental health, suicidality and service use in Queensland, Australia, from 2001 to 2021.

BACKGROUND: The current study aimed to compare current suicide rates, trends, previous treatment, suicidality and mental health diagnoses for First Nations and non-Indigenous young people who died by suicide. METHODS: Age-specific suicide rates (ASSRs) were calculated per 100,000 persons/year using suicides aged 10-19 years in the Queensland Suicide Register. Rate Ratios (RRs) and 95 % CIs compared ASSRs for First Nations and non-Indigenous youth dying by suicide in Queensland, Australia, from 2001 to 2018. Risk ratios (RiskR) with 95 % CIs compared characteristics between First Nations and non-Indigenous youth suicides. Joinpoint regression was used to identify any changes in trends and annual percentage change (APC) in suicides with 95 % CIs. RESULTS: The First Nations youth ASSR was 24.71 deaths per 100,000 persons/year, 4.5 times the non-Indigenous ASSR (95 % CI = 3.74-5.38, p < 0.001). Both non-Indigenous and First Nations suicide trends were stable with no joinpoints (APC: 0.3 %, 95 % CI: -1.6-2.2, p = 0.78; APC: 0.9 %, 95 % CI: -0.2-2.1, p = 0.11). Less than a quarter (23.9 %) of First Nations young people had ever received mental health treatment, significantly fewer than non-Indigenous youth (RiskR = 0.80, 95 % CI = 0.71-0.90, p < 0.001). Similarly, in the three months preceding their death, only 14.5 % of First Nations young people had received mental health treatment (RiskR = 0.89, 95 % CI = 0.83-97, p = 0.015). LIMITATIONS: Reported mental illness, suicidality and help-seeking could be underreported due to concealment from family or police. CONCLUSIONS: The current study finds no change in the gap between the First Nations and Non-Indigenous youth suicide rates nor evidence of decrease in the First Nations youth suicide rate. There is a need for alternative approaches to Indigenous youth suicide prevention, such as assertive outreach models outside of traditional triage and mental health systems to proactively build trusting relationships with young people in communities to identify young people needing support.

DNA statistics in the Simpson matter.

On 3 October 1995, O.J. Simpson was acquitted of two murders in spite of very strong DNA evidence linking his blood to the crime. Although numerical statements describing the strength of this evidence were made, the DNA profiles included so many loci that the need for presenting numbers in this case, and in others using similarly high numbers of loci, is probably unnecessary. If numbers are to be presented, however, they should be given in the form of likelihood ratios. One thing the verdict in the Simpson case makes clear is that it is essential that the integrity of DNA evidence (with regard to collection, potential contamination or tampering) be beyond doubt.

Variation in actual relationship among descendants of inbred individuals.

In previous analyses, the variation in actual, or realized, relationship has been derived as a function of map length of chromosomes and type of relationship, the variation being greater the shorter the total chromosome length and the coefficient of variation being greater the more distant the relationship. Here, the results are extended to allow for the relatives' ancestor being inbred. Inbreeding of a parent reduces variation in actual relationship among its offspring, by an amount that depends on the inbreeding level and the type of mating that led to that level. For descendants of full-sibs, the variation is reduced in later generations, but for descendants of half-sibs, it is increased.

Phylogenetic relationships among global populations of Pseudomonas syringae pv. actinidiae.

ABSTRACT Pseudomonas syringae pv. actinidiae, the causal agent of canker in kiwifruit (Actinidia spp.) vines, was first detected in Japan in 1984, followed by detections in Korea and Italy in the early 1990s. Isolates causing more severe disease symptoms have recently been detected in several countries with a wide global distribution, including Italy, New Zealand, and China. In order to characterize P. syringae pv. actinidiae populations globally, a representative set of 40 isolates from New Zealand, Italy, Japan, South Korea, Australia, and Chile were selected for extensive genetic analysis. Multilocus sequence analysis (MLSA) of housekeeping, type III effector and phytotoxin genes was used to elucidate the phylogenetic relationships between P. syringae pv. actinidiae isolates worldwide. Four additional isolates, including one from China, for which shotgun sequence of the whole genome was available, were included in phylogenetic analyses. It is shown that at least four P. syringae pv. actinidiae MLSA groups are present globally, and that marker sets with differing evolutionary trajectories (conserved housekeeping and rapidly evolving effector genes) readily differentiate all four groups. The MLSA group designated here as Psa3 is the strain causing secondary symptoms such as formation of cankers, production of exudates, and cane and shoot dieback on some kiwifruit orchards in Italy and New Zealand. It is shown that isolates from Chile also belong to this MLSA group. MLSA group Psa4, detected in isolates collected in New Zealand and Australia, has not been previously described. P. syringae pv. actinidiae has an extensive global distribution yet the isolates causing widespread losses to the kiwifruit industry can all be traced to a single MLSA group, Psa3.

Variation in actual relationship as a consequence of Mendelian sampling and linkage.

Although the expected relationship or proportion of genome shared by pairs of relatives can be obtained from their pedigrees, the actual quantities deviate as a consequence of Mendelian sampling and depend on the number of chromosomes and map length. Formulae have been published previously for the variance of actual relationship for a number of specific types of relatives but no general formula for non-inbred individuals is available. We provide here a unified framework that enables the variances for distant relatives to be easily computed, showing, for example, how the variance of sharing for great grandparent-great grandchild, great uncle-great nephew, half uncle-nephew and first cousins differ, even though they have the same expected relationship. Results are extended in order to include differences in map length between sexes, no recombination in males and sex linkage. We derive the magnitude of skew in the proportion shared, showing the skew becomes increasingly large the more distant the relationship. The results obtained for variation in actual relationship apply directly to the variation in actual inbreeding as both are functions of genomic coancestry, and we show how to partition the variation in actual inbreeding between and within families. Although the variance of actual relationship falls as individuals become more distant, its coefficient of variation rises, and so, exacerbated by the skewness, it becomes increasingly difficult to distinguish different pedigree relationships from the actual fraction of the genome shared.

Racial differences in overdose training, naloxone possession, and naloxone administration among clients and nonclients of a syringe services program.

OBJECTIVE: To evaluate racial (Black/White) differences in overdose response training and take-home naloxone (THN) possession and administration among clients and nonclients of the Baltimore syringe service program (SSP). METHODS: The study derived data from a cross-sectional survey of 263 (183 SSP clients, 80 nonclients) people who inject drugs (PWID). The study recruited SSP clients using targeted sampling and recruited nonclients through peer referral from April to November 2016. RESULTS: In our sample, 61% of the participants were Black, 42% were between the ages of 18 and 44, and 70% were males. SSP clients, regardless of race, were more likely to have received overdose response training than Black nonclients (Black clients AOR: 3.85, 95% CI: 1.88, 7.92; White clients AOR: 2.73, 95% CI: 1.29, 5.75). The study found no significant differences in overdose response training between Black and White nonclients. SSP clients and White nonclients were more likely to possess THN than Black nonclients (Black clients: AOR: 4.21, 95% CI: 2.00, 8.87; White clients: AOR: 3.54, 95% CI: 1.56, 8.04; White nonclients AOR: 4.49, 95% CI: 1.50,13.47). CONCLUSION: SSP clients were more likely to receive overdose response training than their nonclient peers who they referred to the study, illustrating the utility of SSPs in reaching PWID at high risk of overdose. We also observed that Black PWID, who did not access services at the SSP, were the least likely to possess THN, suggesting the need to employ outreach targeting Black PWID who do not access this central harm reduction intervention.

Characterizing allelic association in the genome era.

Whole genome data are allowing the estimation of population genetic parameters with an accuracy not imagined 50 years ago. Variation in these parameters along the genome is being found empirically where once only approximate theoretical values were available. Along with increased information, however, has come the issue of multiple testing and the realization that high values of the coefficients of variation of quantities such as relatedness measures may make it difficult to draw inferences. This review concentrates on measures of allelic association within and between individuals and within and between populations.

TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival.

Acquired chromosomal aberrations play an important role in tumour development and progression. Such genetic alterations occur in a significant proportion of non-small cell lung carcinomas (NSCLCs) and include amplification of 14q13.3, which contains the TTF1 gene. We asked whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathological features, including patient survival. We used a FISH assay and quantitative immunohistochemical staining to interrogate a population-based cohort of 538 NSCLCs from Swiss patients for TTF1 amplification and protein expression. We found TTF1 amplification in approximately 13% of adenocarcinomas (ACs) and in approximately 9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumour size, female gender and longer overall survival only among ACs (median survival 82 versus 28 months; p = 0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favourable prognosis in patients with AC [hazard ratio, 0.56 (95% CI 0.38-0.83); p = 0.008]. We conclude that TTF1 amplification is a mechanism of high-level TTF1 expression in a subset of NSCLCs. When expressed at high levels, this routinely used diagnostic marker is also an independent biomarker of favourable prognosis in AC.

Distributions of Hardy-Weinberg equilibrium test statistics.

It is well established that test statistics and P-values derived from discrete data, such as genetic markers, are also discrete. In most genetic applications, the null distribution for a discrete test statistic is approximated with a continuous distribution, but this approximation may not be reasonable. In some cases using the continuous approximation for the expected null distribution may cause truly null test statistics to appear nonnull. We explore the implications of using continuous distributions to approximate the discrete distributions of Hardy-Weinberg equilibrium test statistics and P-values. We derive exact P-value distributions under the null and alternative hypotheses, enabling a more accurate analysis than is possible with continuous approximations. We apply these methods to biological data and find that using continuous distribution theory with exact tests may underestimate the extent of Hardy-Weinberg disequilibrium in a sample. The implications may be most important for the widespread use of whole-genome case-control association studies and Hardy-Weinberg equilibrium (HWE) testing for data quality control.

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272.

Mutations in the ERBB2 gene were recently found in approximately 2% of primary non-small cell lung cancer (NSCLC) specimens; however, little is known about the functional consequences and the relevance to responsiveness to targeted drugs for most of these mutations. Here, we show that the major lung cancer-derived ERBB2 mutants, including the most frequent mutation, A775insYVMA, lead to oncogenic transformation in a cellular assay. Murine cells transformed with these mutants were relatively resistant to the reversible epidermal growth factor receptor (EGFR) inhibitor erlotinib, resembling the resistant phenotype found in cells carrying the homologous mutations in exon 20 of EGFR. However, the same cells were highly sensitive to the irreversible dual-specificity EGFR/ERBB2 kinase inhibitor HKI-272, as were those overexpressing wild-type ERBB2. Finally, the NSCLC cell line, Calu-3, overexpressing wild-type ERBB2 owing to a high-level amplification of the ERBB2 gene were highly sensitive to HKI-272. These results provide a rationale for treatment of patients with ERBB2-mutant or ERBB2-amplified lung tumors with HKI-272.

Bayesian statistics in genetics: a guide for the uninitiated.

Statistical analyses are used in many fields of genetic research. Most geneticists are taught classical statistics, which includes hypothesis testing, estimation and the construction of confidence intervals; this framework has proved more than satisfactory in many ways. What does a Bayesian framework have to offer geneticists? Its utility lies in offering a more direct approach to some questions and the incorporation of prior information. It can also provide a more straightforward interpretation of results. The utility of a Bayesian perspective, especially for complex problems, is becoming increasingly clear to the statistics community; geneticists are also finding this framework useful and are increasingly utilizing the power of this approach.

The Orbiting Carbon Observatory-2 early science investigations of regional carbon dioxide fluxes.

NASA's Orbiting Carbon Observatory-2 (OCO-2) mission was motivated by the need to diagnose how the increasing concentration of atmospheric carbon dioxide (CO2) is altering the productivity of the biosphere and the uptake of CO2 by the oceans. Launched on 2 July 2014, OCO-2 provides retrievals of the column-averaged CO2 dry-air mole fraction ([Formula: see text]) as well as the fluorescence from chlorophyll in terrestrial plants. The seasonal pattern of uptake by the terrestrial biosphere is recorded in fluorescence and the drawdown of [Formula: see text] during summer. Launched just before one of the most intense El Niños of the past century, OCO-2 measurements of [Formula: see text] and fluorescence record the impact of the large change in ocean temperature and rainfall on uptake and release of CO2 by the oceans and biosphere.

DNA commission of the International Society of Forensic Genetics: Recommendations on the interpretation of mixtures.

The DNA commission of the International Society of Forensic Genetics (ISFG) was convened at the 21st congress of the International Society for Forensic Genetics held between 13 and 17 September in the Azores, Portugal. The purpose of the group was to agree on guidelines to encourage best practice that can be universally applied to assist with mixture interpretation. In addition the commission was tasked to provide guidance on low copy number (LCN) reporting. Our discussions have highlighted a significant need for continuing education and research into this area. We have attempted to present a consensus from experts but to be practical we do not claim to have conveyed a clear vision in every respect in this difficult subject. For this reason, we propose to allow a period of time for feedback and reflection by the scientific community. Then the DNA commission will meet again to consider further recommendations.

Statistical analysis of DNA sequences.

Developments in the statistical analysis of DNA sequence data since 1984 are reviewed. Mathematical methods employing dynamic programming or incorporating Markov chain theory have been developed to search sequences for regions of similarity and to align sequences. When the biological forces of mutation and genetic drift are included in models, distances between aligned sequences allow the construction of evolutionary trees. Theory based on models may lead to estimates of variation of parameter estimates and so give a means of assessing the statistical significance of observed patterns and relationships. The complexity of DNA sequences, however, suggests that most statistical inferences will rest on random permutations of sequences.