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The Jacquard genetic identity coefficients are of fundamental importance in relatedness research. We address the estimation of these coefficients as well as other relationship parameters that derive from them such as kinship and inbreeding coefficients using a concise matrix framework. Estimation of the Jacquard coefficients via likelihood methods and the expectation-maximization algorithm is computationally very demanding for large numbers of polymorphisms. We propose a constrained least squares approach to estimate the Jacquard coefficients. A simulation study shows constrained least squares achieves root-mean-squared errors that are comparable with those of the maximum likelihood approach, in particular when founder allele frequencies are unknown, while obtaining enormous computational savings., (© 2024. The Author(s).)

We examine 31,011 PPY23 profiles at the population, metapopulation and world levels. Most haplotypes appear only once but a few have higher counts, including a set of 23 matching profiles in Delhi, India and a set of 16 matching profiles in Burkina Faso with one additional matching American African profile. We estimate F ST values to be used as "theta" (θ) in match probability calculations, following the method we used in our earlier survey of autosomal STR data. Match probability estimates using Fˆ ST or the κ method of Brenner for a previously unseen profile are similar but differ for any profile previously seen., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients ([Formula: see text]) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different [Formula: see text] and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on [Formula: see text] based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator., Competing Interests: Competing interests statement:The authors declare no competing interest.

Population data have become available for sequence data to aid forensic investigations and prepare the forensic community in the move towards implementing NGS methods. This comes with a need for updated population genetic parameters estimates to allow DNA evidence evaluations using sequence data. Initial work has been done on a small sample and here we expand this work by providing estimates of population structure and relatedness for autosomal STR data generated by sequencing technologies. We also discuss the effect of inbreeding on forensic calculations and discuss why the use of genotypic-based estimates may be preferred over allelic-based estimates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Being able to properly quantify genetic differentiation is key to understanding the evolutionary potential of a species. One central parameter in this context is FST, the mean coancestry within populations relative to the mean coancestry between populations. Researchers have been estimating FST globally or between pairs of populations for a long time. More recently, it has been proposed to estimate population-specific FST values, and population-pair mean relative coancestry. Here, we review the several definitions and estimation methods of FST, and stress that they provide values relative to a reference population. We show the good statistical properties of an allele-sharing, method of moments based estimator of FST (global, population-specific and population-pair) under a very general model of population structure. We point to the limitation of existing likelihood and Bayesian estimators when the populations are not independent. Last, we show that recent attempts to estimate absolute, rather than relative, mean coancestry fail to do so., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Goudet, Weir. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the introduction of next generation sequencing (NGS) technology in the forensic field, it will be of interest to assess if forensic scientists feel equipped to interpret and present DNA evidence for sequence data. Here, we describe perceptions of sixteen U.S.-based forensic scientists on statistical models, sequence data, and ethical implications for DNA evidence evaluations. To get an in-depth understanding of the current situation, we used a qualitative research approach with a cross-sectional study design. Semi-structured interviews ( N  = 16) were conducted with U.S. forensic scientists working with DNA evidence. Open-ended interview questions were used to explore participants' views and needs surrounding the use of statistical models and sequence data for forensic purposes. We conducted a conventional content analysis using ATLAS. ti software and employed a second coder to ensure reliability of our results. Eleven themes emerged: 1) a statistical model that maximizes the value of the evidence is preferred; 2) a high-level understanding of the statistical model used is generally sufficient; 3) transparency is key in minimizing the risk of creating black boxes; 4) training and education should be an ongoing effort; 5) the effectiveness of presenting results in court can be improved; 6) NGS has the potential to become revolutionary; 7) some hesitations surrounding the use of sequence data remain; 8) there is a need for a concrete plan to alleviate barriers to the implementation of sequencing techniques; 9) ethics plays a major part in the role of a forensic scientist; 10) ethical barriers for sequence data depend on the application; 11) DNA evidence has its limitations. The results of this study give insight into the perceptions of forensic scientists regarding the use of statistical models and sequence data, providing valuable information in the move towards implementing sequencing methods for DNA evidence evaluations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Isolates of a variety of fungal plant pathogens ( Alternaria radicina ICMP 5619, Cercospora beticola ICMP 15907, Dactylonectria macrodidyma ICMP 16789, D. torresensis ICMP 20542, Ilyonectria europaea ICMP 16794, and I. liriodendra ICMP 16795) were screened for antimicrobial activity against the human pathogenic bacteria Acinetobacter baumannii , Pseudomonas aeruginosa , Escherichia coli , Mycobacterium abscessus , and M. marinum and were found to have some activity. Investigation of the secondary metabolites of these fungal isolates led to the isolation of ten natural products ( 1-10 ) of which one was novel, ( E )-4,7-dihydroxyoct-2-enoic acid ( 1 ). Structure elucidation of all natural products was achieved by a combination of NMR spectroscopy and mass spectrometry. We also investigated the antimicrobial activity of a number of the isolated natural products. While we did not find ( E )-4,7-dihydroxyoct-2-enoic acid ( 1 ) to have any activity against the bacteria and fungi in our assays, we did find that cercosporin ( 7 ) exhibited potent activity against Methicillin resistant Staphylococcus aureus (MRSA), dehydro-curvularin ( 6 ) and radicicol ( 10 ) exhibited antimycobacterial activity against M. marinum , and brefeldin A ( 8 ) and radicicol ( 10 ) exhibited antifungal activity against Candida albicans . Investigation of the cytotoxicity and haemolytic activities of these natural products ( 6-8 and 10 ) found that only one of the four active compounds, radicicol ( 10 ), was non-cytotoxic and non-haemolytic.

A new calculation module within the PopStats module of the CODIS software package, based on the underlying mathematics presented in the MixKin software package, has been developed for assigning the Likelihood Ratio (LR) of DNA mixture profiles. This module uses a semi-continuous model that allows for population structure and allelic drop-out and drop-in but does not require allelic peak heights or other laboratory-specific parameters. This new implementation (named SC Mixture), like MixKin, does not specify or estimate a probability of drop-out. Instead, each contributor to a mixture has an independent drop-out rate, and the probability of the mixture profile for a specified proposition concerning the contributors is integrated over the range of possible drop-out rates. The allelic drop-in rate and the population structure parameter, theta, used by the software are specified by the user. The user can examine up to five contributors to a mixture, however, conditioning on assumed contributors and limiting the number of unknowns in both numerator and denominator hypotheses greatly improves performance. We report results from an extensive validation study performed for ten mixtures with each of one (single source), two, three, four, or five contributors, with four combinations of drop-in rate and a population structure parameter. Each mixture was run as a complete profile or with the random removal of alleles to simulate drop-out. All 1620 combinations were evaluated with PopStats, MixKin, and LRmix and considerable consistency was found among the results with all three packages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Kākāpō are a critically endangered species of parrots restricted to a few islands off the coast of New Zealand. Kākāpō are very closely monitored, especially during nesting seasons. In 2019, during a highly successful nesting season, an outbreak of aspergillosis affected 21 individuals and led to the deaths of 9, leaving a population of only 211 kākāpō. In monitoring this outbreak, cultures of aspergillus were grown, and genome sequenced. These sequences demonstrate that, very unusually for an aspergillus outbreak, a single strain of aspergillus caused the outbreak. This strain was found on two islands, but only one had an outbreak of aspergillosis; indicating that the strain was necessary, but not sufficient, to cause disease. Our analysis provides an understanding of the 2019 outbreak and provides potential ways to manage such events in the future., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Antimicrobial compounds, including antibiotics, have been a cornerstone of modern medicine being able to both treat infections and prevent infections in at-risk people, including those who are immune-compromised and those undergoing routine surgical procedures. Their intense use, including in people, animals, and plants, has led to an increase in the incidence of resistant bacteria and fungi, resulting in a desperate need for novel antimicrobial compounds with new mechanisms of action. Many antimicrobial compounds in current use originate from microbial sources, such as penicillin from the fungus Penicillium chrysogenum (renamed by some as P. rubens ). Through a collaboration with Aotearoa New Zealand Crown Research Institute Manaaki Whenua-Landcare Research we have access to a collection of thousands of fungal cultures known as the International Collection of Microorganisms from Plants (ICMP). The ICMP contains both known and novel species which have not been extensively tested for their antimicrobial activity. Initial screening of ICMP isolates for activity against Escherichia coli and Staphylococcus aureus directed our interest towards ICMP 477, an isolate of the soil-inhabiting fungus, Aspergillus terreus . In our investigation of the secondary metabolites of A. terreus , through extraction, fractionation, and purification, we isolated nine known natural products. We evaluated the biological activity of selected compounds against various bacteria and fungi and discovered that terrein ( 1 ) has potent activity against the important human pathogen Cryptococcus neoformans ., Competing Interests: Siouxsie Wiles is an Academic Editor for PeerJ., (© 2022 Cadelis et al.)

The quantitative geneticist W. G. ('Bill') Hill, awardee of the 2018 Darwin Medal of the Royal Society and the 2019 Mendel Medal of the Genetics Society (United Kingdom), died on 17 December 2021 at the age of 81 years. Here, we pay tribute to his multiple key scientific contributions, which span population and evolutionary genetics, animal and plant breeding and human genetics. We discuss his theoretical research on the role of linkage disequilibrium (LD) and mutational variance in the response to selection, the origin of the widely used LD metric r 2 in genomic association studies, the genetic architecture of complex traits, the quantification of the variation in realized relationships given a pedigree relationship and much more. We demonstrate that basic theoretical research in quantitative and statistical genetics has led to profound insights into the genetics and evolution of complex traits and made predictions that were subsequently empirically validated, often decades later., (© 2022. Springer Nature America, Inc.)

In his 1972 paper 'The apportionment of human diversity', Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low F ST values. However, when we analyse haplotypes defined by these SNPs (which define 'HLA alleles'), we find marked differences in frequencies between geographic regions. These differences are not reflected in the F ST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting F ST . Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.

The Hardy-Weinberg law is shown to be transitive in the sense that a multi-allelic polymorphism that is in equilibrium will retain its equilibrium status if any allele together with its corresponding genotypes is deleted from the population. Similarly, the transitivity principle also applies if alleles are joined, which leads to the summation of allele frequencies and their corresponding genotype frequencies. These basic polymorphism properties are intuitive, but they have apparently not been formalized or investigated. This article provides a straightforward proof of the transitivity principle, and its usefulness in genetic data analysis is explored, using high-quality autosomal microsatellite databases from the US National Institute of Standards and Technology. We address the reduction of multi-allelic polymorphisms to variants with fewer alleles, two in the limit. Equilibrium test results obtained with the original and reduced polymorphisms are generally observed to be coherent, in particular when results obtained with length-based and sequence-based microsatellites are compared. We exploit the transitivity principle in order to identify disequilibrium-related alleles, and show its usefulness for detecting population substructure and genotyping problems that relate to null alleles and allele imbalance., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Biological collections preserve our past, while helping protect our future and increase future knowledge. Plant bacterial culture collections are our security for domestic and global biosecurity. This feature article will provide an introduction to the global position of plant bacterial collections. The role of collections in monitoring plant pathogenic bacteria will be explored through the presentation of five cases studies. These case studies demonstrate why culture collections were imperative for the outcome in each situation. We discuss what we believe should be the best practices to improve microbial preservation and accessioning rates, and why plant bacterial culture collections must increase deposits to be prepared for future emerging pathogens. This is not only the case for global culture collections, but on a much bigger scale, our future scientific successes, our biosecurity decisions and responses, and our knowledge are contingent upon preserving our valuable bacterial strains. It is hoped that once you read this article, you will see the need to deposit your strains in registered public collections and make a concerted effort to build better bacterial culture collections with us.

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Transnational ivory traffickers continue to smuggle large shipments of elephant ivory out of Africa, yet prosecutions and convictions remain few. We identify trafficking networks on the basis of genetic matching of tusks from the same individual or close relatives in separate shipments. Analyses are drawn from 4,320 savannah (Loxodonta africana) and forest (L. cyclotis) elephant tusks, sampled from 49 large ivory seizures totalling 111 t, shipped out of Africa between 2002 and 2019. Network analyses reveal a repeating pattern wherein tusks from the same individual or close relatives are found in separate seizures that were containerized in, and transited through, common African ports. Results suggest that individual traffickers are exporting dozens of shipments, with considerable connectivity between traffickers operating in different ports. These tools provide a framework to combine evidence from multiple investigations, strengthen prosecutions and support indictment and prosecution of transnational ivory traffickers for the totality of their crimes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The two alleles an individual carries at a locus are identical by descent (ibd) if they have descended from a single ancestral allele in a reference population, and the probability of such identity is the inbreeding coefficient of the individual. Inbreeding coefficients can be predicted from pedigrees with founders constituting the reference population, but estimation from genetic data is not possible without data from the reference population. Most inbreeding estimators that make explicit use of sample allele frequencies as estimates of allele probabilities in the reference population are confounded by average kinships with other individuals. This means that the ranking of those estimates depends on the scope of the study sample and we show the variation in rankings for common estimators applied to different subdivisions of 1000 Genomes data. Allele-sharing estimators of within-population inbreeding relative to average kinship in a study sample, however, do have invariant rankings across all studies including those individuals. They are unbiased with a large number of SNPs. We discuss how allele sharing estimates are the relevant quantities for a range of empirical applications., (© 2021. The Author(s).)

Screening of several fungi from the New Zealand International Collection of Microorganisms from Plants identified two strains of Penicillium, P. bissettii and P. glabrum , which exhibited antimicrobial activity against Escherichia coli, Klebsiella pneumoniae , and Staphylococcus aureus. Further investigation into the natural products of the fungi, through extraction and fractionation, led to the isolation of five known polyketide metabolites, penicillic acid ( 1 ), citromycetin ( 2 ), penialdin A ( 3 ), penialdin F ( 4 ), and myxotrichin B ( 5 ). Semi-synthetic derivatization of 1 led to the discovery of a novel dihydro ( 1a ) derivative that provided evidence for the existence of the much-speculated open-chained form of 1 . Upon investigation of the antimicrobial activities of the natural products and derivatives, both penicillic acid ( 1 ) and penialdin F ( 4 ) were found to inhibit the growth of Methicillin-resistant S. aureus . Penialdin F ( 4 ) was also found to have some inhibitory activity against Mycobacterium abscessus and M. marinum along with citromycetin ( 2 ).

Introduction: The purpose of this quality improvement project was to develop and evaluate the use of an electronic medication request dashboard to reduce the amount of time required for medication processing and decrease time lost to workflow interruptions during patient discharge. Delayed discharges are associated with increased health care costs and adverse patient outcomes. Processing of medication requests at discharge contributes to these delays and to workflow interruptions for nursing and pharmacy staff at the project site. Electronic dashboards have been successfully implemented in multiple medical settings to streamline patient processing and enhance communication., Materials and Methods: The Human Protections Office at Carl R. Darnall Army Medical Center (Fort Hood, TX) reviewed and approved the project with a non-human research determination. A multi-disciplinary workgroup with representatives from nursing, pharmacy, and health information technology (HIT) was formed to develop the dashboard. Based on a logic flow diagram of the desired communication, HIT created a medication request form and status dashboard using SharePoint and Nintex workflows. The dashboard was implemented for a 30-day pilot on a 25-bed medical/surgical nursing unit. The time required for medication processing, the time from discharge order to patient exit, the number of phone calls between nursing and pharmacy, and the usability of the medication request process were measured before and after implementation. The results were analyzed with descriptive statistics and evaluated for statistical significance with a P value ≤.05., Results: With implementation of the dashboard, the average medication processing time decreased from 125 minutes to 48 minutes (P < .0001), and the average patient discharge time decreased from 137 minutes to 117 minutes (P = .002). The usability score of the medication request process increased from 40 to 87 for nursing (P < .0001) and from 62 to 85 for pharmacy (P = .003). The total number of voice calls between nursing and pharmacy decreased from 1,115 to 434, while the total time on voice calls decreased from 33 hours and 50 minutes to 13 hours and 19 minutes (P < .0001)., Conclusions: The electronic dashboard is an effective method to enhance interdisciplinary communication during patient discharge and significantly reduces medication processing times. However, despite the medication processing time decreasing by over an hour, the discharge time only decreased by 20 minutes. Additional investigation is needed to evaluate other contributors to delayed discharge. A key limitation of this study was the convenience sampling used over a 30-day pilot on a single unit. The process has since been adopted by the entire hospital, and additional analysis could better reveal the impact to the organization. This communication system shows high usability and reduces phone call interruptions for both nursing and pharmacy staff. Additionally, this technology could easily be applied to other communication pathways or request processes across military medicine., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

There is a real and urgent need for new antibiotics able to kill Mycobacteria, acid-fast bacilli capable of causing multiple deadly diseases. These include members of the Mycobacterium tuberculosis complex, which causes the lung disease tuberculosis (TB) as well as non-tuberculous Mycobacteria (NTM) a growing cause of lung, skin, soft tissue, and other infections. Here we describe a medium-throughput bioluminescence-based pipeline to screen fungi for activity against Mycobacteria using the NTM species Mycobacterium abscessus and Mycobacterium marinum. We used this pipeline to screen 36 diverse fungal isolates from the International Collection of Microorganisms from Plants (ICMP) grown on a wide variety of nutrient-rich and nutrient-poor media and discovered that almost all the tested isolates produced considerable anti-mycobacterial activity. Our data also provides strong statistical evidence for the impact of growth media on antibacterial activity. Chemical extraction and fractionation of a subset of the ICMP isolates revealed that much of the activity we observed may be due to the production of the known anti-mycobacterial compound linoleic acid. However, we have identified several ICMP isolates that retained their anti-mycobacterial activity in non-linoleic acid containing fractions. These include isolates of Lophodermium culmigenum , Pseudaegerita viridis , and Trametes coccinea , as well as an unknown species of Boeremia and an isolate of an unknown genus and species in the family Phanerochaetaceae . Investigations are ongoing to identify the sources of their anti-mycobacterial activity and to determine whether any may be due to the production of novel bioactive compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grey, Cadelis, Diao, Park, Lumley, Weir, Copp and Wiles.)

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae . Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae . Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris ). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium . Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae . Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae ( e.g. , Cosmosporella , Macroconia , Microcera ). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium . To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa ( act1 , CaM , his3 , rpb1 , rpb2 , tef1 , tub2 , ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella ) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [ F. dimerum species complex (SC)], Cyanonectria ( F. buxicola SC), Geejayessia ( F. staphyleae SC), Neocosmospora ( F. solani SC) or Rectifusarium ( F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org)., (© 2021 Westerdijk Fungal Biodiversity Institute. Production and hosting by ELSEVIER B.V.)

Fungi have become an invaluable source of bioactive natural products, with more than 5 million species of fungi spanning the globe. Fractionation of crude extract of Neodidymelliopsis sp., led to the isolation of a novel polyketide, (2 Z )-cillifuranone ( 1 ) and five previously reported natural products, (2 E )-cillifuranone ( 2 ), taiwapyrone ( 3 ), xylariolide D ( 4 ), pachybasin ( 5 ), and N -(5-hydroxypentyl)acetamide ( 6 ). It was discovered that (2 Z )-cillifuranone ( 1 ) was particularly sensitive to ambient temperature and light resulting in isomerisation to (2 E )-cillifuranone ( 2 ). Structure elucidation of all the natural products were conducted by NMR spectroscopic techniques. The antimicrobial activity of 2 , 3 , and 5 were evaluated against a variety of bacterial and fungal pathogens. A sodium [1- 13 C] acetate labelling study was conducted on Neodidymelliopsis sp. and confirmed that pachybasin is biosynthesised through the acetate polyketide pathway.

Slow growing oomycete isolates with morphological resemblance to Phytophthora were obtained from forest streams during routine monitoring for the EU quarantine forest pathogen Phytophthora ramorum in Ireland and Northern Ireland. Internal Transcribed Spacer (ITS) sequence analysis indicated that they belonged to two previously unknown species of Nothophytophthora, a recently erected sister genus of Phytophthora. Morphological and temperature-growth studies were carried out to characterise both new species. In addition, Bayesian and Maximum-Likelihood analyses of nuclear 5-loci and mitochondrial 3-loci datasets were performed to resolve the phylogenetic positions of the two new species. Both species were sterile, formed chlamydospores and partially caducous nonpapillate sporangia, and showed slower growth than any of the six known Nothophytophthora species. In all phylogenetic analyses both species formed distinct, strongly supported clades, closely related to N. chlamydospora and N. valdiviana from Chile. Based on their unique combination of morphological and physiological characters and their distinct phylogenetic positions the two new species are described as Nothophytophthora irlandica sp. nov. and N. lirii sp. nov. Their potential lifestyle and geographic origin are discussed., Competing Interests: The authors have declared that no competing interests exist.

Antimicrobial bioassay-guided fractionation of the endophytic fungi Neofusicoccum australe led to the isolation of a new unsymmetrical naphthoquinone dimer, neofusnaphthoquinone B ( 1 ), along with four known natural products ( 2 - 5 ). Structure elucidation was conducted by nuclear magnetic resonance (NMR) spectroscopic methods, and the antimicrobial activity of all the natural products was investigated, revealing 1 to be moderately active towards methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 16 µg/mL.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes) 1 . In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

Taxonomic and functional research of microorganisms has increasingly relied upon genome-based data and methods. As the depository of the Global Catalogue of Microorganisms (GCM) 10K prokaryotic type strain sequencing project, Global Catalogue of Type Strain (gcType) has published 1049 type strain genomes sequenced by the GCM 10K project which are preserved in global culture collections with a valid published status. Additionally, the information provided through gcType includes >12 000 publicly available type strain genome sequences from GenBank incorporated using quality control criteria and standard data annotation pipelines to form a high-quality reference database. This database integrates type strain sequences with their phenotypic information to facilitate phenotypic and genotypic analyses. Multiple formats of cross-genome searches and interactive interfaces have allowed extensive exploration of the database's resources. In this study, we describe web-based data analysis pipelines for genomic analyses and genome-based taxonomy, which could serve as a one-stop platform for the identification of prokaryotic species. The number of type strain genomes that are published will continue to increase as the GCM 10K project increases its collaboration with culture collections worldwide. Data of this project is shared with the International Nucleotide Sequence Database Collaboration. Access to gcType is free at http://gctype.wdcm.org/., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with "ethnicity" or "race") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as "Black" and "Mixed" on average have lower chances of finding matches than those who self-identify as "White" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary., (Copyright © 2020 Nunes, Aguiar, Silva, Sena, de Oliveira, Dinardo, Kehdy, Tarazona-Santos, Rocha, Carneiro-Proietti, Loureiro, Flor-Park, Maximo, Kelly, Custer, Weir, Sabino, Porto and Meyer.)

Match probabilities calculated during the evaluation of DNA evidence profiles rely on appropriate values of the population structure quantity θ. NGS-based methods will enhance forensic identification and with the transformation to such methods comes the need to facilitate NGS-based population genetics analysis. If NGS data are to be used for match probabilities there needs to be a way to accommodate population structure, which requires values for θ for those data. Such estimates have not been available. This study assesses population structure for sequence-based data using a relatively new approach applied to STR data over 27 loci in five different geographic groups. Matching proportions between individuals or groups are used to obtain locus-specific θ estimates as well as estimates per geographic group and a global measure. The results demonstrate similar effects of sequencing data on θ estimates compared to what has been seen for CE-based results., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Antimicrobial bioassay-guided fractionation of Microcera larvarum led to the isolation of a γ-lactone with a furo[3,4- b ]pyran-5-one bicyclic ring system ( 1 ) and three known compounds, (3 S ,4 R )-4-hydroxymellein ( 2 ), (3 S ,4 S )-4-hydroxymellein ( 3 ) and 7-hydroxy-3-(1-hydroxyethyl)isobenzofuran-1(3 H )-one ( 4 ). Structure elucidation was conducted by NMR spectroscopic methods. Absolute configuration of 1 (2 R , 3 S , 5 S , 7 S, 8 R ) was established using the chiral derivatizing agent MPA and was fully supported by calculated specific rotation and ECD spectra. The spectroscopic data observed for 1 were identical to those previously reported for theissenolactone A ( 7 ), necessitating a correction of the latter (from C-5/C-8 trans ring fusion to cis ). Compounds 1 - 4 were evaluated for antimicrobial activity against a panel of pathogens.