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Novel species of fungi described in this study include those from various countries as follows: Australia , Agaricus albofoetidus , Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii , Keissleriella sporoboli from stem of Sporobolus natalensis , Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis , Serendipita petricolae as endophyte from roots of Eriochilus petricola , Stagonospora tauntonensis from stem of Sporobolus natalensis , Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada , Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic , Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France , Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India , Amanita konajensis on soil and Keithomyces indicus from soil. Israel , Microascus rothbergiorum from Stylophora pistillata. Italy , Calonarius ligusticus on soil. Netherlands , Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus , Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella , Myrmecridium phragmitigenum on dead culm of Phragmites australis , Neochalara lolae on stems of Pteridium aquilinum , Niesslia nieuwwulvenica on dead culm of undetermined Poaceae , Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway , Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal , Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa , Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain , Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum , Geoglossum lauri-silvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa , Terfezia bertae and Tuber davidlopezii in soil. Sweden , Alpova larskersii , Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand , Russula banwatchanensis , Russula purpureoviridis and Russula lilacina on soil. Ukraine : Crous PW, Boers J, Holdom D, et al. 2022. Fungal Planet description sheets: 1383-1435. Persoonia 48: 261-371. https://doi.org/10.3767/persoonia.2022.48.08.Nectriella adonidis on overwintered stems of Adonis vernalis. USA , Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes. Citation : Crous PW, Boers J, Holdom D, et al. 2022. Fungal Planet description sheets: 1383-1435. Persoonia 48: 261-371. https://doi.org/10.3767/persoonia.2022.48.08., (© 2022 Naturalis Biodiversity Center & Westerdijk Fungal Biodiversity Institute.)

The mating-type (MAT1) locus encodes transcription factors essential for the onset of the sexual cycle in ascomycete fungi. This locus has been characterised in only a few heterothallic, plant pathogenic Mycosphaerellaceae and Teratosphaeriaceae. We used available genome sequences for Mycosphaerellales species to investigate the presence of two unique mating-type-associated features. The accessory MAT1 genes, MAT1-1-10 (MATORF2) and MAT1-2-12 (MATORF1), typically occurred in both MAT idiomorphs of Mycosphaerellaceae species. In contrast, they were associated with only one idiomorph in Teratosphaeriaceae species. In Pseudocercospora, phylogenetic analyses showed that homologs present in different idiomorphs were paralogous and subject to different selective pressures, indicating that their evolution is linked to mating type. In almost half of the investigated Mycosphaerellales genomes, numerous short fragment sequences, almost identical to portions of the MAT1-1-1 and MAT1-2-1 genes, were present in multiple areas outside of the MAT1 locus. Aligned to the MAT1 genes, these sequences resembled an mRNA transcript. Fragment sequences were similar among species groups and occurred at the same genomic positions, implying that monophyletic groups have the same origins of these sequences. Although the functions of the MAT fragment sequences and accessory MAT1 genes remain unknown, both were expressed in the representative Mycosphaerellaceae and Teratosphaeriaceae species that were investigated., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Contamination in sequenced genomes is a relatively common problem and several methods to remove non-target sequences have been devised. Typically, the target and contaminating organisms reside in different kingdoms, simplifying their separation. The authors present the case of a genome for the ascomycete fungus Teratosphaeria eucalypti , contaminated by another ascomycete fungus and a bacterium. Approaching the problem as a low-complexity metagenomics project, the authors used two available software programs, BlobToolKit and anvi'o, to filter the contaminated genome. Both the de novo and reference-assisted approaches yielded a high-quality draft genome assembly for the target fungus. Incorporating reference sequences increased assembly completeness and visualization elucidated previously unknown genome features. The authors suggest that visualization should be routine in any sequencing project, regardless of suspected contamination.

Teratosphaeria destructans is one of the most aggressive foliar pathogens of Eucalyptus. The biological factors underpinning T. destructans infections, which include shoot and leaf blight on young trees, have never been interrogated. Thus, the means by which the pathogen modifies its host environment to overcome host defences remain unknown. By applying transcriptome sequencing, the aim of this study was to compare gene expression in a South African isolate of T. destructans grown on nitrogen-deficient and complete media. This made it possible to identify upregulated genes in a nitrogen-starved environment, often linked to the pathogenicity of the fungus. The results support the hypothesis that nitrogen starvation in T. destructans likely mirrors an in planta genetic response. This is because 45% of genes that were highly upregulated under nitrogen starvation have previously been reported to be associated with infection in other pathogen systems. These included several CAZymes, fungal effector proteins, peptidases, kinases, toxins, lipases and proteins associated with detoxification of toxic compounds. Twenty-five secondary metabolites were identified and expressed in both nitrogen-deficient and complete conditions. Additionally, the most highly expressed genes in both growth conditions had pathogenicity-related functions. This study highlights the large number of expressed genes associated with pathogenicity and overcoming plant defences. As such, the generated baseline knowledge regarding pathogenicity and aggressiveness in T. destructans is a valuable reference for future in planta work., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

D-serine is an endogenous co-agonist with glutamate for activation of the N -methyl-D-aspartate receptor (NMDAR). D-serine exacerbates neuronal death and is elevated in the spinal cord from patients with sporadic/familial ALS. The present study was undertaken to examine whether plasma levels of D-serine of patients with ALS are different from those of healthy controls. Levels of D-serine in plasma (30 patients and 30 controls) were measured by high-performance liquid chromatography mass spectrometry. Plasma levels of D-serine in ALS patients (mean 39.27 ± 28.61 ng/ml) were significantly higher ( p  = 0.0293) than those of healthy control subjects (mean 21.07 ± 14.03 ng/ml) as well as previously reported values for healthy controls; ∼43% of patients had plasma D-serine levels that were 2 to 4-folds higher than those of controls. There was no association of plasma D-serine levels with disability, the duration of disease or with the age of subjects. In conclusion, we show that D-serine levels are elevated in the plasma of some ALS patients. Since D-serine serves as a co-agonist/activator of NMDAR, increases in D-serine could have a direct influence on glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.

Draft genomes of the fungal species Ambrosiella cleistominuta , Cercospora brassicicola, C. citrullina, Physcia stellaris, and Teratosphaeria pseudoeucalypti are presented. Physcia stellaris is an important lichen forming fungus and Ambrosiella cleistominuta is an ambrosia beetle symbiont. Cercospora brassicicola and C. citrullina are agriculturally relevant plant pathogens that cause leaf-spots in brassicaceous vegetables and cucurbits respectively. Teratosphaeria pseudoeucalypti causes severe leaf blight and defoliation of Eucalyptus trees. These genomes provide a valuable resource for understanding the molecular processes in these economically important fungi., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Teratosphaeria destructans is an aggressive fungal pathogen causing leaf and shoot blight on young Eucalyptus trees in plantations. The disease occurs across tropical and subtropical regions of South East Asia and has recently been found in South Africa. Asexual structures of the pathogen are produced on infected tissues, but sexual structures have never been observed. The aim of this study was to investigate the reproductive biology of T. destructans by characterising its mating type (MAT1) locus and investigating its potential for sexual recombination. We found that T. destructans has a heterothallic mating system, with either the MAT1-1-1 and MAT1-1-10 genes (MAT1-1 idiomorph) or the MAT1-2-1 and MAT1-2-12 genes (MAT1-2 idiomorph) present in a single individual. With a multiplex PCR assay, it was possible to distinguish the two MAT idiomorphs in several Teratosphaeria species and this approach was applied to six global populations of T. destructans. Although both mating types occurred in the South East Asian populations, a single mating type dominated each population. Isolates from the recent disease outbreak in South Africa comprised only a single mating type. Attempts to induce a sexual cycle in vitro using strains of opposite mating type were not successful. The uneven distribution of mating types in populations of T. destructans and the presence of only an asexual state on infected tissues suggests the absence of or at least a minor role for sexual reproduction where the pathogen occurs on non-native Eucalyptus in plantations., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to determine whether patients with amyotrophic lateral sclerosis (ALS) exhibit higher plasma levels of formaldehyde (FA) than controls, and to look for alterations in levels of FA precursors., Methods: We studied 40 heathy controls and 50 ALS patients from the Motor Neuron Disease clinic at the Royal Brisbane & Women's Hospital. Plasma FA levels were quantified using a FA detection assay. Trimethylamine (TMA) and trimethylamine oxide (TMAO) in plasma were quantified by multiple reaction monitoring (MRM) mass spectrometry. Plasma levels in patients and controls were compared using Mann-Whitney U test and Spearman's correlation test was used to assess the correlation between levels of FA, TMA, TMAO and other variables., Results: The levels of plasma FA were significantly greater in ALS subjects than controls. TMA and TMAO levels were not significantly different between healthy controls and patients, but were greater in ALS subjects with elevated FA levels than those with normal levels. Of note, levels of TMA and TMAO demonstrated a significant positive correlation with plasma FA levels (spearman's correlation coefficients of TMA with FA [r = 0.451, p = 0.010] and TMAO [r = 0.401, p = 0.023]). There was no association of FA levels with disability measured with the ALS functional rating scale, with the duration of disease or with the age of the subjects., Conclusion: Elevated FA is found in some patients with ALS. FA is neurotoxic and could contribute to disease pathogenesis., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest. The authors alone are responsible for the content and paper writing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Mood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal-human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety., Methods: Adult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time - the drift diffusion model (DDM) - from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards., Results: Both groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction., Conclusions: Humans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

Objectives: Excitotoxicity is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). One possible source of excitotoxicity is the presence of sulphur amino acids (SAAs). In the brain of subjects with ALS, there are increased levels of taurine. In the metabolism of methionine to taurine, excitatory sulphur amino acids (SAAs) are formed. These could potentially contribute to excitotoxicity in ALS. The present study has examined whether plasma levels of SAAs in 38 ALS patients differ from those of 30 healthy controls., Methods: Plasma levels of SAAs were measured by liquid chromatography mass spectrometry., Results: There were no significant changes in plasma cysteic acid, cysteine sulfinic acid, and homocysteic acid in ALS patients compared to healthy subjects. Significant elevations in plasma homocysteinesulfinic acid (HCSA) levels (p < 0.0001) were observed in the ALS patients (75.91 ± 15.38 nM) compared to healthy controls (54.06 ± 8.503 nM); 50% of the ALS patients had HCSA levels that were 1.5-2-folds higher than those of controls. Plasma levels of HCSA differed significantly (p = 0.0440) between patients with bulbar onset and spinal onset (68.57 ± 14.20 vs. 79.30 ± 14.95 nM, respectively)., Conclusion: HCSA is elevated in the blood of subjects with ALS. Since HCSA can be transported from the blood to the CNS by active transport, has neurotransmitter properties, and can activate synaptic receptors including NMDAR and metabotropic glutamate receptor, it is possible that increases in HCSA could influence glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Anxiety is characterized by altered responses under uncertain conditions, but the precise mechanism by which uncertainty changes the behaviour of anxious individuals is unclear. Here we probe the computational basis of learning under uncertainty in healthy individuals and individuals suffering from a mix of mood and anxiety disorders. Participants were asked to choose between four competing slot machines with fluctuating reward and punishment outcomes during safety and stress. We predicted that anxious individuals under stress would learn faster about punishments and exhibit choices that were more affected by those punishments, thus formalizing our predictions as parameters in reinforcement learning accounts of behaviour. Overall, the data suggest that anxious individuals are quicker to update their behaviour in response to negative outcomes (increased punishment learning rates). When treating anxiety, it may therefore be more fruitful to encourage anxious individuals to integrate information over longer horizons when bad things happen, rather than try to blunt their responses to negative outcomes.

Dysfunctional memory processes are widely reported in anxiety disorders, but the underlying neurocognitive mechanisms are unclear. Recent work shows that the impact of anxiety on memory depends on the context and memory modality. For instance, threat of shock, a translational within-subject anxiety induction, has been shown to impair the encoding of facial stimuli, while improving spatial working memory (WM) accuracy. The present study aimed to delineate the neural circuitry regulating these opposing behavioural effects. Thirty-three healthy volunteers performed the previously assessed facial recognition and a spatial WM tasks inside an fMRI scanner, under alternating within-subject conditions of threat or safe from shock across encoding and retrieval. Facial recognition impairments were replicated when threat was selectively induced at encoding. Neuroimaging results suggest that this effect was driven by increased competition for attentional resources within the anterior cingulate cortex, in which activation correlated positively with stress levels. The impact of threat on spatial WM performance did not, however, replicate in the fMRI environment. Nevertheless, state-dependent hippocampal activation was observed in both tasks. These findings suggest a neurocognitive mechanism by which anxiety impairs facial recognition as well as a state-dependent hippocampal activation pattern, which may putatively underline retrieval of negative experiences in anxiety., (© The Author(s) 2019. Published by Oxford University Press.)

Draft genomes of the fungal species Fusarium xylarioides, Teratosphaeria gauchensis and T. zuluensis are presented. In addition an annotation of the genome of Ceratocystis fimbriata is presented. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity and potential management strategies of these economically important fungi., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Background: Teratosphaeria gauchensis and T. zuluensis are closely related fungi that cause Teratosphaeria (previously Coniothyrium) stem canker disease on Eucalyptus species propagated in plantations for commercial purposes. This disease is present in many countries in which Eucalyptus trees are planted, and continues to spread with the international trade of infected plant germplasm., Taxonomy: Fungi, Ascomycota, Pezizomycotina, Dothideomycetes, Dothideomycetidae, Capnodiales, Teratosphaeriaceae, Teratosphaeria., Identification: The causal agents form dark masses of pycnidia that are visible on the surface of distinct stem cankers that typically form on young green stem tissues. Accurate diagnosis of the causal agents requires DNA sequence data., Host Range: Nine species of Eucalyptus are known to be affected. Of these, E. grandis and its hybrids, which include some of the most important planting stock globally, appear to be particularly vulnerable., Disease Symptoms: Small necrotic lesions develop on young green stem tissue. These lesions coalesce to form large cankers that exude gum. Epicormic shoots develop below the girdling canker and, in severe cases, trees die., Useful Websites: Mycobank, https://www.mycobank.org; Publications of the Forestry and Agricultural Biotechnology Institute (FABI), https://www.fabinet.up.ac.za/index.php/journals., (© 2018 The Authors. Molecular Plant Pathology Published by BSPP and John Wiley & Sons Ltd.)

Genome comparisons of species with distinctive ecological traits can elucidate genetic divergence that influenced their differentiation. The interaction of a microorganism with its biotic environment is largely regulated by secreted compounds, and these can be predicted from genome sequences. In this study, we considered Knoxdaviesia capensis and Knoxdaviesia proteae, two closely related saprotrophic fungi found exclusively in Protea plants. We investigated their genome structure to compare their potential inter-specific interactions based on gene content. Their genomes displayed macrosynteny and were approximately 10 % repetitive. Both species had fewer secreted proteins than pathogens and other saprotrophs, reflecting their specialized habitat. The bulk of the predicted species-specific and secreted proteins coded for carbohydrate metabolism, with a slightly higher number of unique carbohydrate-degrading proteins in the broad host-range K. capensis. These fungi have few secondary metabolite gene clusters, suggesting minimal competition with other microbes and symbiosis with antibiotic-producing bacteria common in this niche. Secreted proteins associated with detoxification and iron sequestration likely enable these Knoxdaviesia species to tolerate antifungal compounds and compete for resources, facilitating their unusual dominance. This study confirms the genetic cohesion between Protea-associated Knoxdaviesia species and reveals aspects of their ecology that have likely evolved in response to their specialist niche., (Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

This genome announcement includes draft genomes from Claviceps purpurea s.lat., including C. arundinis , C. humidiphila and C. cf. spartinae . The draft genomes of Davidsoniella eucalypti, Quambalaria eucalypti and Teratosphaeria destructans, all three important eucalyptus pathogens, are presented. The insect associate Grosmannia galeiformis is also described. The pine pathogen genome of Fusarium circinatum has been assembled into pseudomolecules, based on additional sequence data and by harnessing the known synteny within the Fusarium fujikuroi species complex. This new assembly of the F. circinatum genome provides 12 pseudomolecules that correspond to the haploid chromosome number of F. circinatum . These are comparable to other chromosomal assemblies within the FFSC and will enable more robust genomic comparisons within this species complex.

Perceptual constancy strongly relies on adaptive gain control mechanisms, which shift perception as a function of recent sensory history. Here we examined the extent to which individual differences in magnitude of adaptation aftereffects for social and non-social directional cues are related to autistic traits and sensory sensitivity in healthy participants (Experiment 1); and also whether adaptation for social and non-social directional cues is differentially impacted in adults with Autism Spectrum Disorder (ASD) relative to neurotypical (NT) controls (Experiment 2). In Experiment 1, individuals with lower susceptibility to adaptation aftereffects, i.e. more 'veridical' perception, showed higher levels of autistic traits across social and non-social stimuli. Furthermore, adaptation aftereffects were predictive of sensory sensitivity. In Experiment 2, only adaptation to eye-gaze was diminished in adults with ASD, and this was related to difficulties categorizing eye-gaze direction at baseline. Autism Diagnostic Observation Schedule (ADOS) scores negatively predicted lower adaptation for social (head and eye-gaze direction) but not non-social (chair) stimuli. These results suggest that the relationship between adaptation and the broad socio-cognitive processing style captured by 'autistic traits' may be relatively domain-general, but in adults with ASD diminished adaptation is only apparent where processing is most severely impacted, such as the perception of social attention cues., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Serious and debilitating symptoms of anxiety are the most common mental health problem worldwide, accounting for around 5% of all adult years lived with disability in the developed world. Avoidance behavior-avoiding social situations for fear of embarrassment, for instance-is a core feature of such anxiety. However, as for many other psychiatric symptoms the biological mechanisms underlying avoidance remain unclear., Methods: Reinforcement learning models provide formal and testable characterizations of the mechanisms of decision making; here, we examine avoidance in these terms. A total of 101 healthy participants and individuals with mood and anxiety disorders completed an approach-avoidance go/no-go task under stress induced by threat of unpredictable shock., Results: We show an increased reliance in the mood and anxiety group on a parameter of our reinforcement learning model that characterizes a prepotent (pavlovian) bias to withhold responding in the face of negative outcomes. This was particularly the case when the mood and anxiety group was under stress., Conclusions: This formal description of avoidance within the reinforcement learning framework provides a new means of linking clinical symptoms with biophysically plausible models of neural circuitry and, as such, takes us closer to a mechanistic understanding of mood and anxiety disorders., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Both human papillomavirus (HPV) vaccination and screening/treatment are relatively simple and inexpensive to implement at all resource levels, and cervical cancer screening has been acknowledged as a "best buy" by the WHO. However, coverage with these interventions is low where they are needed most. Failure to launch or expand cervical cancer prevention programs is by and large due to the absence of dedicated funding, along with a lack of recognition of the urgent need to update policies that can hinder access to services. Clear and sustained communication, robust advocacy, and strategic partnerships are needed to inspire national governments and international bodies to action, including identifying and allocating sustainable program resources. There is significant momentum for expanding coverage of HPV vaccination and screening/preventive treatment in low-resource settings as evidenced by new global partnerships espousing this goal, and the participation of groups that previously had not focused on this critical health issue., (© 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Anxiety disorders are associated with disruptions in both emotional processing and decision making. As a result, anxious individuals often make decisions that favor harm avoidance. However, this bias could be driven by enhanced aversion to uncertainty about the decision outcome (e.g., risk) or aversion to negative outcomes (e.g., loss). Distinguishing between these possibilities may provide a better cognitive understanding of anxiety disorders and hence inform treatment strategies., Methods: To address this question, unmedicated individuals with pathological anxiety (n = 25) and matched healthy control subjects (n = 23) completed a gambling task featuring a decision between a gamble and a safe (certain) option on every trial. Choices on one type of gamble-involving weighing a potential win against a potential loss (mixed)-could be driven by both loss and risk aversion, whereas choices on the other type-featuring only wins (gain only)-were exclusively driven by risk aversion. By fitting a computational prospect theory model to participants' choices, we were able to reliably estimate risk and loss aversion and their respective contribution to gambling decisions., Results: Relative to healthy control subjects, pathologically anxious participants exhibited enhanced risk aversion but equivalent levels of loss aversion., Conclusions: Individuals with pathological anxiety demonstrate clear avoidance biases in their decision making. These findings suggest that this may be driven by a reduced propensity to take risks rather than a stronger aversion to losses. This important clarification suggests that psychological interventions for anxiety should focus on reducing risk sensitivity rather than reducing sensitivity to negative outcomes per se., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Studying the effects of experimentally induced anxiety in healthy volunteers may increase our understanding of the mechanisms underpinning anxiety disorders. Experimentally induced stress (via threat of unpredictable shock) improves accuracy at withholding a response on the sustained attention to response task (SART), and in separate studies improves accuracy to classify fearful faces, creating an affective bias. Integrating these findings, participants at two public science engagement events ( n  = 46, n  = 55) were recruited to explore the effects of experimentally induced stress on an affective version of the SART. We hypothesized that we would see an improved accuracy at withholding a response to affectively congruent stimuli (i.e. increased accuracy at withholding a response to fearful 'no-go' distractors) under threat of shock. Induced anxiety slowed reaction time, and at the second event quicker responses were made to fearful stimuli. However, we did not observe improved inhibition overall during induced anxiety, and there was no evidence to suggest an interaction between induced anxiety and stimulus valence on response accuracy. Indeed Bayesian analysis provided decisive evidence against this hypothesis. We suggest that the presence of emotional stimuli might make the safe condition more anxiogenic, reducing the differential between conditions and knocking out any threat-potentiated improvement., Competing Interests: We declare we have no competing interests.

The majority of plant pathogens are fungi and many of these adversely affect food security. This mini-review aims to provide an analysis of the plant pathogenic fungi for which genome sequences are publically available, to assess their general genome characteristics, and to consider how genomics has impacted plant pathology. A list of sequenced fungal species was assembled, the taxonomy of all species verified, and the potential reason for sequencing each of the species considered. The genomes of 1090 fungal species are currently (October 2016) in the public domain and this number is rapidly rising. Pathogenic species comprised the largest category (35.5 %) and, amongst these, plant pathogens are predominant. Of the 191 plant pathogenic fungal species with available genomes, 61.3 % cause diseases on food crops, more than half of which are staple crops. The genomes of plant pathogens are slightly larger than those of other fungal species sequenced to date and they contain fewer coding sequences in relation to their genome size. Both of these factors can be attributed to the expansion of repeat elements. Sequenced genomes of plant pathogens provide blueprints from which potential virulence factors were identified and from which genes associated with different pathogenic strategies could be predicted. Genome sequences have also made it possible to evaluate adaptability of pathogen genomes and genomic regions that experience selection pressures. Some genomic patterns, however, remain poorly understood and plant pathogen genomes alone are not sufficient to unravel complex pathogen-host interactions. Genomes, therefore, cannot replace experimental studies that can be complex and tedious. Ultimately, the most promising application lies in using fungal plant pathogen genomics to inform disease management and risk assessment strategies. This will ultimately minimize the risks of future disease outbreaks and assist in preparation for emerging pathogen outbreaks.

: Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic hematopoietic stem cell transplantation, which is a potential curative therapy used in a variety of malignant or benign hematological diseases. Graft-versus-host disease primarily occurs in many organs, but most notably in the skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal system. Ocular manifestations of GVHD may precede other systemic GVHD findings, and it may be a poor prognosis for mortality. While all parts of the eye may be affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or keratoconjunctivitis sicca is the most common presenting manifestation of chronic ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability. Depending on the severity of ocular involvement and response to treatment, ocular GVHD may cause decreased quality of life. Management of GVHD begins with prevention by understanding risk factors and by implementing prophylactic treatment after allogeneic hematopoietic stem cell transplantation. A multidisciplinary approach to the prevention and treatment of GVHD is important, and there are currently no preventive therapies available for ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular surface lubrication and support, tear film stabilization, inflammation reduction, and surgical intervention. The goal of this review is to define ocular GVHD and its categorical manifestations, as well as to describe the importance of comprehensive assessment, diagnosis, and ophthalmologic treatment and management of ocular GVHD with a multidisciplinary approach.

Response to stress or external threats is a key factor in mood and anxiety disorder aetiology. Current measures of anxious responding to threats are limited because they largely rely on retrospective self-report. Objectively quantifying individual differences in threat response would be a valuable step towards improving our understanding of anxiety disorder vulnerability. Our goal is to therefore develop a reliable, objective, within-subject 'stress-test' of anxious responding. To this end, we examined threat-potentiated performance on an inhibitory control task from baseline to 2-4 weeks (n = 50) and again after 5-9 months (n = 22). We also describe single session data for a larger sample (n = 157) to provide better population-level estimates of task performance variance. Replicating previous findings, threat of shock improved distractor accuracy and slowed target reaction time on our task. Critically, both within-subject self-report measures of anxiety (ICC = 0.66) and threat-potentiated task performance (ICC = 0.58) showed clinically useful test-retest reliability. Threat-potentiated task performance may therefore hold promise as a non-subjective measure of individual anxious responding.

Sexual reproduction is necessary to generate genetic diversity and, in ascomycete fungi, this process is controlled by a mating type (MAT) locus with two complementary idiomorphs. Knoxdaviesia capensis and K. proteae (Sordariomycetes; Microascales; Gondwanamycetaceae) are host-specific saprophytic fungi that show high population diversity within their Protea plant hosts in the Cape Floristic Region of South Africa. We hypothesise that this diversity is the result of outcrossing driven by a heterothallic mating system and sought to describe the MAT1 loci of both species. The available genome assembly of each isolate contained only one of the MAT1 idiomorphs necessary for sexual reproduction, implying that both species are heterothallic. Idiomorph segregation during meiosis, a 1:1 ratio of idiomorphs in natural populations and mating experiments also supported heterothallism as a sexual strategy. Long-range PCR and shot-gun sequencing to identify the opposite idiomorph in each species revealed no sequence similarity between MAT1-1 and MAT1-2 idiomorphs, but the homologous idiomorphs between the species were almost identical. The MAT1-1 idiomorph contained the characteristic MAT1-1-1 and MAT1-1-2 genes, whereas the MAT1-2 idiomorph consisted of the genes MAT1-2-7 and MAT1-2-1. This gene content was similar to that of the three species in the Ceratocystidaceae (Microascales) with characterized MAT loci. The Knoxdaviesia MAT1-2-7 protein contained and alpha domain and predicted intron, which suggests that this gene arose from MAT1-1-1 during a recombination event. In contrast to the Ceratocystidaceae species, Knoxdaviesia conformed to the ancestral Sordariomycete arrangement of flanking genes and is, therefore, a closer reflection of the structure of this locus in the Microascalean ancestor., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Two polyphyletic genera of ophiostomatoid fungi are symbionts of Proteaceae in southern Africa. One of these, Knoxdaviesia, includes two closely related species, K. proteae and K. capensis, that have overlapping geographical distributions, but are not known to share Protea host species. Knoxdaviesia capensis appears to be a generalist that occupies numerous hosts, but has never been found in P. repens, the only known host of K. proteae. In this study, extensive collections were made from P. repens and isolates were identified using DNA sequence comparisons. This led to the surprising discovery of K. capensis from P. repens for the first time. The fungus was encountered at a low frequency, suggesting that P. repens is not its preferred host, which may explain why it has not previously been found on this plant. The basis for the specialisation of K. proteae and K. capensis on different Protea species remains unknown.

Reports of sensory disturbance, such as loudness sensitivity or sound intolerance, are ubiquitous in Autism Spectrum Disorder (ASD) but a mechanistic explanation for these perceptual differences is lacking. Here we tested adaptation to loudness, a process that regulates incoming sensory input, in adults with ASD and matched controls. Simple loudness adaptation (SLA) is a fundamental adaptive process that reduces the subjective loudness of quiet steady-state sounds in the environment over time, whereas induced loudness adaptation (ILA) is a means of generating a reduction in the perceived volume of louder sounds. ASD participants showed a striking reduction in magnitude and rate of SLA relative to age and ability-matched typical adults, but in contrast ILA remained intact. Furthermore, rate of SLA predicted sensory sensitivity coping strategies in the ASD group. These results provide the first evidence that compromised neural mechanisms governing fundamental adaptive processes might account for sound sensitivity in ASD.

Background: Eccrine porocarcinoma (EPC) has a poor prognosis after standard wide local excision (WLE), with 20% local recurrence, 20% regional and 12% distant metastatic rates. Mohs micrographic surgery (MMS) has been used as a promising treatment., Objective: To review the use of MMS for EPC and assess treatment outcomes., Materials and Methods: This was a retrospective case series of 12 EPC patients treated by MMS between 1984 and 2013 in the institution. Furthermore, a literature review revealed an additional 17 cases of EPC managed by MMS., Results: Of 29 cases of EPC treated by MMS, outcome was established in 27 cases. The patients had a significantly longer mean follow-up period of 6 years (range, 4-206 months), as compared with 19 months (range, 2-48 months) in reported cases. Two patients had regional lymph node metastasis after MMS. The regional metastatic rates to lymph nodes were 7% (2/27). There was no local recurrence, distant metastasis, or disease-specific death in the 27 cases studied., Conclusion: To the best of the authors' knowledge, this is the single largest case series of EPCs treated by MMS and the authors' data demonstrated that MMS may be superior to the standard WLE.

The Fynbos Biome in the Core Cape Subregion of South Africa is prone to recurrent fires that can clear vast areas of vegetation. Between periods of fire, ophiostomatoid fungi colonize the fruiting structures of serotinous Protea species through arthropod-mediated dispersal. Using microsatellite markers, this study considered the process whereby a Protea-associated ophiostomatoid fungus, Knoxdaviesia proteae, recolonizes a burnt area. The genetic diversity, composition and structure of fungal populations from young P. repens plants in a recently burnt area were compared to populations from the adjacent, unburnt Protea population. The only difference between K. proteae populations from the two areas was found in the number of private alleles, which was significantly higher in the unburnt population. The population structure, although weak, indicated that most K. proteae individuals from recently burnt areas originated from the unburnt population. However, individuals from unsampled source populations were also detected. This, together with the lack of isolation-by-distance across the landscape, suggested that long-distance dispersal is important for K. proteae to recolonize burnt areas. Similarly, the high level of gene flow and low differentiation observed between two distantly separated K. proteae populations also supported the existence of long-distance dispersal. The genetic cohesiveness of populations over long distances and the genetic diversity within populations could be attributed to frequent multiple fungal migration events mediated primarily by arthropods but, potentially, also by birds., (Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Knoxdaviesia proteae, a fungus specific to the floral structures of the iconic Cape Floral Kingdom plant, Protea repens, is dispersed by mites phoretic on beetles that pollinate these flowers. Although the vectors of K. proteae have been identified, little is known regarding its patterns of distribution. Seed bearing infructescences of P. repens were sampled from current and previous flowering seasons, from which K. proteae individuals were isolated and cultured. The genotypes of K. proteae isolates were determined using 12 microsatellite markers specific to this species. Genetic diversity indices showed a high level of similarity between K. proteae isolates from the two different infructescence age classes. The heterozygosity of the population was high (0.74 ± 0.04), and exceptional genotypic diversity was encountered (Ĝ = 97.87%). Population differentiation was negligible, owing to the numerous migrants between the infructescence age classes (N m = 47.83) and between P. repens trees (N m = 2.96). Parsimony analysis revealed interconnected genotypes, indicative of recombination and homoplasies, and the index of linkage disequilibrium confirmed that outcrossing is prevalent in K. proteae ([Formula: see text] = 0.0067; P = 0.132). The high diversity and panmixia in this population is likely a result of regular gene flow and an outcrossing reproductive strategy. The lack of genetic cohesion between individuals from a single P. repens tree suggests that K. proteae dispersal does not primarily occur over short distances via mites as hypothesized, but rather that long-distance dispersal by beetles plays an important part in the biology of these intriguing fungi.

Background: While patients' hypertensive problems are usually actively and effectively managed by their primary physician, the dermatologic surgeon can still be affected by hypertension where the condition is unrecognized or uncontrolled. Hypertension is an important contributor to both bleeding and hematoma formation during and after surgery, ultimately affecting functional and cosmetic outcomes., Objective: To extensively review the literature on perioperative management of the hypertensive patient as relates to the dermatologic surgeon., Materials and Methods: An updated and comprehensive literature review, focusing on current diagnostic guidelines, practice by specific dermatologic surgery groups and management recommendations, was conducted., Results: Review of the literature does support generalized guidelines for the management of hypertensive patients in the Mohs Micrographic Surgery (MMS) setting; however data on implementation and outcomes by specific dermatologic surgery groups is variable and lacking., Conclusions: The treatment of nonmelanoma skin cancers with MMS is now routine, and fortunately can be performed quite safely. There are still improvements to be made however, in managing perioperative hypertension-both in making patients aware of their condition and in treating it effectively. Practicing these measures can promote patients' overall health and the efficiency of the dermatologic surgeon's practice.

Background: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers., Objective: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC)., Methods: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 μL of E. peplus sap once daily for 3 days., Results: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9)., Conclusions: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Acylation of 3-O-angeloylingenol (1) with vinyl acetate, vinyl decanoate and vinyl cinnamate, catalyzed by Candida antarctica Lipase B, was investigated. In each case, compound 1 was quantitatively and regioselectively acylated to afford a single product, 3-O-angeloyl-20-O-acetylingenol (1a), 3-O-angeloyl-20-O-decanoylingenol (1b) and 3-O-angeloyl-20-O-cinnamoylingenol (1c), respectively. The structures of the novel compounds 1b-1c were determined by MS and NMR, and product 1a by comparison of RP-HPLC and TLC with a standard. Compounds 1b-1c induced a bipolar morphology of MM96L melanoma cells at a similar concentration as compound 1, as well as having activity in inhibiting the growth of MM96L melanoma cells.

Objectives: The objective of this study was to develop and pretest a questionnaire to assess the practice of withdrawal of life-sustaining treatment in the NICU on the basis of the experiences of bereaved parents., Methods: We conducted semistructured interviews with 11 parents whose infants had undergone withdrawal of life-sustaining treatment in the NICU at McMaster University Medical Centre to obtain their views on helpful practices. Interviews continued until no new items were obtained (ie, saturation point). A total of 370 items were distilled into 82 questionnaire statements on care by a multidisciplinary team and grouped for analysis into 6 domains: communication, quality of care, quality of life, shared decision-making, withdrawal of life-sustaining treatment process, and bereavement care. Respondents were asked to rank how frequently events occurred on a 7-point Likert scale anchored from 1 = never to 7 = always. A score of >5 was considered favorable. The questionnaire was distributed to a pretest sample of perinatal social workers who attended a bereavement workshop at an international conference., Results: The response rate was 48%. Respondents ranked items that pertained to the withdrawal of life-sustaining treatment process highest, indicating that items were done well. Items related to quality of care and bereavement care ranked lowest. Other domains ranked as follows: communication, shared decision-making, and quality of life. Consistency of items within domains was tested by Cronbach's alpha and split-half testing and were >0.6 for most domains., Conclusions: Parents' views on important aspects of end-of-life care in the NICU were incorporated into a quality assurance questionnaire. Pretesting assessed the performance of the instrument and the perceptions of social workers on the effectiveness of end-of-life practices. Respondents identified that parents' practical needs were met during the withdrawal process but were not consistently met in regard to the quality of in-hospital and follow-up bereavement care.

Aims: To obtain reliable transformation of a range of Butyrivibrio fibrisolvens strains and to express a Neocallimastix patriciarum xylanase gene in the recipients., Methods and Results: Eight strains (H17c, E14, LP1309, LP1028, AR11a, OB156, LP210B and LP461A) of Bu. fibrisolvens were transformed by the Gram-positive vector pUB110. A xylanase expression/secretion cassette containing Bu. fibrisolvens promoter and signal peptide elements fused to catalytic domain II of the N. patriciarum xylanase A cDNA (xynANp) was inserted into pUB110 to create the plasmid pUBxynA. pUBxynA was used to transform seven of the Bu. fibrisolvens strains transformed by pUB110. In strain H17c pUBxynA, which produced native xylanase, 2.46 U mg-1 total xylanase activity was produced with 45% extracellular xylanase. In strain H17c pUMSX, 0.74 U mg-1 total xylanase activity was produced with 98% extracellular xylanase. H17c pUBxynA exhibited increased (28.7%) degradation of neutral detergent fibre compared with unmodified H17c; however, progressive loss of pUBxynA was observed in long-term cultivation., Conclusions: A stable transformation system was developed that was applicable for a range of Bu. fibrisolvens strains and high levels of expression of a recombinant xylanase were obtained in H17c which lead to increased fibre digestion., Significance and Impact of the Study: This stable transformation system with the accompanying recombinant plasmids will be a useful tool for further investigation aimed at improving ruminal fibre digestion.

Temperature-regulated expression of recombinant proteins in the tac promoter (Ptac) system was investigated. Expression levels of fungal xylanase and cellulase from N. patriciarum in E. coli strains containing the natural lacI gene under the control of the Ptac markedly increased with increasing cultivation temperature in the absence of a chemical inducer. The specific activities (units per milligram protein of crude enzyme) of the fungal xylanase and cellulase produced from recombinant E. coli strain pop2136 grown at 42 degrees C were about 4.5 times higher than those of the cells grown at 23 degrees C and were even slightly higher when compared with cells grown in the presence of the inducer isopropyl beta-D-thiogalactopyranoside. The xylanase expression level in the temperature-regulated Ptac system was about 35% of total cellular protein. However, this system can not be applied to E. coli strains containing lacIq, which confers over production of the lac repressor, for high-level expression of recombinant proteins. In comparison with the lambda PL system, the Ptac-based xylanase plasmid in E. coli pop2136 gave a considerably higher specific activity of the xylanase than did the best lambda PL-based construct using the same thermal induction procedure. The high-level expression of the xylanase using the temperature-regulated Ptac system was also obtained in 10-litre fermentation studies using a fed-batch process. These results unambiguously demonstrated that the temperature-modulated Ptac system can be used for overproduction of some non-toxic recombinant proteins.

A Neocallimastix patriciarum xylanase cDNA with the core coding sequence essentially identical to xynA was isolated and modified for high-level expression in Escherichia coli. The xylanase cDNA was truncated into individual catalytic domains, which were modified at the N-terminus. These modified xylanases were synthesised as non-fusion proteins under the control of the tac promoter. High-level expression was obtained with the modified domain II construct, accounting for approx. 25% of total cellular protein. However, with the same vector and expression cassette, expression levels of constructs containing domain I or domains I and II fused in tandem were very low. RNA analysis revealed that the striking difference in expression levels of these three constructs was not due to transcription efficiency, but was mainly related to transcript stability. Further analysis of the domain II construct revealed that the high-level expression of the domain II xylanase was largely attributed to the presence of a favourable N-terminal coding sequence, as mutation at the N-terminus of the domain II dramatically reduced the expression level. The modified domain II xylanase produced in E. coli had a specific activity of 1229 U mg-1 protein at pH 7 and 50 degrees C without purification. The availability of a recombinant fungal xylanase with high specific activity and in high yield offers a potentially attractive source of xylanase for industrial applications.

Background: During the past 10 years there has been an increase in the use of the antimalarial agents, chloroquine and hydroxychloroquine, in the treatment of various rheumatic diseases., Methods: In the United States, hydroxychloroquine (Plaquenil) is one of the most commonly prescribed medications for mild to moderately severe rheumatoid arthritis. Both chloroquine and hydroxychloroquine have the potential to produce an irreversible maculopathy. However, this maculopathy occurs almost exclusively at higher than recommended doses., Results: Careful dose monitoring by the rheumatologist, combined with appropriate ocular examination by the eye care professional, can significantly reduce the risk of retinopathy., Conclusions: This paper discusses the use of chloroquine and hydroxychloroquine in the treatment of rheumatoid arthritis and systemic lupus erythematosus, it summarizes their retinotoxic risk, and it outlines the diagnostic techniques used to evaluate patients treated with these medications.

A cDNA expression library of the rumen fungus Neocallimastix patriciarum was made in Escherichia coli. Cellulolytic clones were identified by screening on a medium containing carboxymethylcellulose. Restriction mapping and Southern hybridization analysis of selected clones revealed three distinct cellulase cDNAs, designated celA, celB and celC. Studies on the substrate specificity showed that the enzyme encoded by celA had high activity towards amorphous and microcrystalline cellulose, while the celB and celC enzymes had relatively high activity on carboxymethylcellulose, with little activity on microcrystalline cellulose. Analysis of hydrolysis products from defined cellodextrins showed that the celB and celC enzymes hydrolysed beta-1,4-glucosidic linkages randomly, whereas the celA enzyme cleaved cellotetraose to cellobiose, and cellopentaose to cellobiose and cellotriose. Cellobiose was also the only product detectable from hydrolysis of microcrystalline cellulose by the celA enzyme. Based on substrate specificity and catalytic mode, celA appears to encode a cellobiohydrolase, while celB and celC encode endoglucanases. Northern blot hybridization analysis showed that expression of the three cellulase transcripts in N. patriciarum was induced by cellulose.