Genomic and genetic insights into a cosmopolitan fungus, Paecilomyces variotii (Eurotiales)

Species in the genus Paecilomyces, a member of the fungal order Eurotiales, are ubiquitous in nature and impact a variety of human endeavors. Here, the biology of one common species, Paecilomyces variotii, was explored using genomics and functional genetics. Sequencing the genome of two isolates revealed key genome and gene features in this species. A striking feature of the genome was the two-part nature, featuring large stretches of DNA with normal GC content separated by AT-rich regions, a hallmark of many plant-pathogenic fungal genomes. These AT-rich regions appeared to have been mutated by repeat-induced point (RIP) mutations. We developed methods for genetic transformation of P. variotii, including forward and reverse genetics as well as crossing techniques. Using transformation and crossing, RIP activity was identified, demonstrating for the first time that RIP is an active process within the order Eurotiales. A consequence of RIP is likely reflected by a reduction in numbers of genes within gene families, such as in cell wall degradation, and reflected by growth limitations on P. variotii on diverse carbon sources. Furthermore, using these transformation tools we characterized a conserved protein containing a domain of unknown function (DUF1212) and discovered it is involved in pigmentation.Peer reviewe

Draft genome sequences of three monokaryotic isolates of the white-rot basidiomycete fungus Dichomitus squalens

Peer reviewe

A MultiCenter analysis of factors associated with hearing outcome for 2,735 adults with cochlear implants

While the majority of cochlear implant recipients benefit from the device, it remains difficult to estimate the degree of benefit for a specific patient prior to implantation. Using data from 2,735 cochlear-implant recipients from across three clinics, the largest retrospective study of cochlear-implant outcomes to date, we investigate the association between 21 preoperative factors and speech recognition approximately one year after implantation and explore the consistency of their effects across the three constituent datasets. We provide evidence of 17 statistically significant associations, in either univariate or multivariate analysis, including confirmation of associations for several predictive factors, which have only been examined in prior smaller studies. Despite the large sample size, a multivariate analysis shows that the variance explained by our models remains modest across the datasets (R2 = 0.12–0.21). Finally, we report a novel statistical interaction indicating that the duration of deafness in the implanted ear has a stronger impact on hearing outcome when considered relative to a candidate’s age. Our multicenter study highlights several real-world complexities that impact the clinical translation of predictive factors for cochlear implantation outcome. We suggest several directions to overcome these challenges and further improve our ability to model patient outcomes with increased accuracy.The collection of the VUMC dataset was supported by a research project grant no. NIH NIDCD R01 DC13117 (principal investigator: Gifford).http://journals.sagepub.com/home/tiadm2022Speech-Language Pathology and Audiolog

Predictive models for cochlear implant outcomes : performance, generalizability, and the impact of cohort size

While cochlear implants have helped hundreds of thousands of individuals, it remains difficult to predict the extent to which an individual’s hearing will benefit from implantation. Several publications indicate that machine learning may improve predictive accuracy of cochlear implant outcomes compared to classical statistical methods. However, existing studies are limited in terms of model validation and evaluating factors like sample size on predictive performance. We conduct a thorough examination of machine learning approaches to predict word recognition scores (WRS) measured approximately 12 months after implantation in adults with post-lingual hearing loss. This is the largest retrospective study of cochlear implant outcomes to date, evaluating 2,489 cochlear implant recipients from three clinics. We demonstrate that while machine learning models significantly outperform linear models in prediction of WRS, their overall accuracy remains limited (mean absolute error: 17.9-21.8). The models are robust across clinical cohorts, with predictive error increasing by at most 16% when evaluated on a clinic excluded from the training set. We show that predictive improvement is unlikely to be improved by increasing sample size alone, with doubling of sample size estimated to only increasing performance by 3% on the combined dataset. Finally, we demonstrate how the current models could support clinical decision making, highlighting that subsets of individuals can be identified that have a 94% chance of improving WRS by at least 10% points after implantation, which is likely to be clinically meaningful. We discuss several implications of this analysis, focusing on the need to improve and standardize data collection.http://journals.sagepub.com/home/tiadm2022Speech-Language Pathology and Audiolog

A comparative genomics study of 23 Aspergillus species from section Flavi

Section Flavi encompasses both harmful and beneficial Aspergillus species, such as Aspergillus oryzae, used in food fermentation and enzyme production, and Aspergillus flavus, food spoiler and mycotoxin producer. Here, we sequence 19 genomes spanning section Flavi and compare 31 fungal genomes including 23 Flavi species. We reassess their phylogenetic relationships and show that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans and identify high genome diversity, especially in sub-telomeric regions. We predict abundant CAZymes (598 per species) and prolific secondary metabolite gene clusters (73 per species) in section Flavi. However, the observed phenotypes (growth characteristics, polysaccharide degradation) do not necessarily correlate with inferences made from the predicted CAZyme content. Our work, including genomic analyses, phenotypic assays, and identification of secondary metabolites, highlights the genetic and metabolic diversity within section Flavi.Peer reviewe

Conserved white-rot enzymatic mechanism for wood decay in the Basidiomycota genus Pycnoporus

White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here, we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood-decaying activity within the Basidiomycota genus Pycnoporus. We observed a strong conservation in the genome structures and the repertoires of protein-coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analysed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2-producing enzymes with H2O2-consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 lytic polysaccharide monooxygenase gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood-decaying process.Peer reviewe

Factors influencing post-implantation hearing ability of adult cochlear implant candidates with pre-operative acoustic hearing

© 2016 Dr. Kerrie Lynne PlantIt is becoming increasingly common for adults with significant residual acoustic hearing in one or both ears to attend cochlear implant centres for candidature assessment. The clinical decision-making and provision of recommendations regarding this candidate population is complex, because there are only limited clinical data currently available to assist with counselling of candidates regarding expected outcomes. Pre- and post-implantation (3, 6 and 12-month) measures were obtained for 65 subjects who were implanted unilaterally in the poorer ear, and who had significant pre-operative acoustic hearing in one or both ears. This research first investigated outcomes in relation to the potential risks associated with implantation of such candidates; (1) the risk to loss of acoustic hearing in the implanted ear for candidates with pre-operative bilateral acoustic hearing, (2) the potential for less post-implantation benefit in candidates with better contralateral hearing, and (3) the unknown influence of predictive factors in this expanded population. In (3) were included the influence of demographic and hearing configuration, as well as an aspect of post-operative device fitting relating to the degree of match between the assigned acoustic input frequency in the sound processor and the electrical pitch percept. Finally, the factors that influenced the electrical pitch percept were examined. Significant group mean post-implantation improvement was observed on a sentence-in-coincident babble test and for spatial release from masking advantage when the noise location favoured the implanted side. Self-reported group ratings of functional benefit were improved post-implantation for all questionnaires administered. Objective assessment revealed poorer group mean localisation ability post-operatively for subjects with pre-operative bilateral acoustic hearing, however subjective ratings in real-world environments were more variable. Degree of post-implantation SRT benefit on the coincident babble test and on self-reported ratings of perception of soft speech and sounds in the environment was greater for subjects with less contralateral hearing. Factors that predicted better unilateral word scores in quiet (and accounted for 34.1% of the variance) were a shorter duration of severe-to-profound hearing loss in the implanted ear and poorer pure-tone-averaged thresholds in the contralateral ear. A shorter duration of severe-to-profound hearing loss in the implanted ear, a lower age at the time of implantation, and better contralateral hearing thresholds were associated with higher bilateral word recognition in quiet and SRT in noise (and accounted for 36.0% and 30.9% of the variance respectively). Degree of match between the initial (pre-activation) pitch percept elicited from stimulation on the most apical channel and the assigned frequency affected rate of post-operative improvement in the unilateral but not bimodal device configuration. Post-experience measures revealed higher unilateral word in quiet and sentence in babble scores for those subjects with closer match between the assigned acoustic input frequency and electrical pitch percept. No significant correlation was observed between degree of match and bilateral speech recognition ability. Subjects with poorer hearing in the implanted ear tended to have a lower pitch and a shallow electrical pitch function than predicted by the spiral ganglion frequency-position model. There was no significant group effect of listening experience

Fitting recommendations and clinical benefit associated with use of the NAL-NL2 hearing-aid prescription in Nucleus cochlear implant recipients

Objective: For a group of cochlear implant recipients, who use hearing aids in the contralateral ear, the benefit of NAL-NL2 relative to a recipients’ own prescription was assessed. Whether there was a preferred frequency response and/or gain deviation from NAL-NL2 was then investigated. Design: Speech recognition and self-reported ratings of benefit were examined for the recipients’ own prescription compared to the NAL-NL2 prescription, in the bimodal and hearing-aid alone conditions. Paired-comparison of hearing-aid frequency response was conducted with default NAL-NL2 and two variants, a low frequency boost or cut. Using a loudness balancing procedure, the hearing-aid gain required to achieve equal loudness between the devices was measured. Study sample: Sixteen adults with post-lingual hearing loss. Results: A 22% increase in group median word score in quiet with use of NAL-NL2 in the hearing-aid alone condition. In the bimodal condition there was no improvement with NAL-NL2. Default NAL-NL2 frequency response was preferred by 67% of participants. For 56% of participants, the preferred gain to achieve loudness balance across bimodal devices was within 5-dB of prescribed values. Conclusions: The NAL-NL2 prescription provides a high level of clinical performance, and an acceptable frequency response and gain for most participants.6 page(s

Influence of contralateral acoustic hearing on adult bimodal outcomes after cochlear implantation

Objective: To examine post-implantation benefit and time taken to acclimate to the cochlear implant for adult candidates with more hearing in the contralateral non-implanted ear than has been previously considered within local candidacy guidelines. Design: Prospective, within-subject experimental design. Study sample: Forty postlingual hearing-impaired adult subjects with a contralateral ear word score in quiet ranging from 27% to 100% (median 67%). Results: Post-implantation improvement of 2.4 dB and 4.0 dB was observed on a sentence in coincident babble test at presentation levels of 65 and 55 dB SPL respectively, and a 2.1 dB benefit in spatial release from masking (SRM) advantage observed when the noise location favoured the implanted side. Significant post-operative group mean change of between 2.1 and 3.0 was observed on the sub-scales of the speech, spatial, and qualities (SSQ) questionnaire. Degree of post-implantation speech reception threshold (SRT) benefit on the coincident babble test and on perception of soft speech and sounds in the environment was greater for subjects with less contralateral hearing. The degree of contralateral acoustic hearing did not affect time taken to acclimate to the device. Conclusions: The findings from this study support cochlear implantation for candidates with substantial acoustic hearing in the contralateral ear, and provide guidance regarding post-implantation expectations.11 page(s

Factors predicting postoperative unilateral and bilateral speech recognition in adult cochlear implant recipients with acoustic hearing

Objectives: The first objective was to examine factors that could be predictive of postoperative unilateral (cochlear implant alone) speech recognition ability in a group of subjects with greater degrees of preoperative acoustic hearing than has been previously examined. Second, the study aimed to identify factors predictive of speech recognition in the best-aided, bilateral listening condition. Design: Participants were 65 postlinguistically hearing-impaired adults with preoperative phoneme in quiet scores of greater than or equal to 46% in one or both ears. Preoperative demographic and audiometric factors were assessed as predictors of 12-month postoperative unilateral and bilateral monosyllabic word scores in quiet and of bilateral speech reception threshold (SRT) in babble. Results: The predictive regression model accounted for 34.1% of the variance in unilateral word recognition scores in quiet. Factors that predicted better scores included: a shorter duration of severe to profound hearing loss in the implanted ear; and poorer pure-tone-averaged thresholds in the contralateral ear. Predictive regression models of postimplantation bilateral function accounted for 36.0% of the variance for word scores in quiet, and 30.9% of the variance for SRT in noise. A shorter duration of severe to profound hearing loss in the implanted ear, a lower age at the time of implantation, and better contralateral hearing thresholds were associated with higher bilateral word recognition in quiet and SRT in noise. Conclusions: In this group of cochlear implant recipients with preoperative acoustic hearing, a shorter duration of severe to profound hearing loss in the implanted ear was shown to be predictive of better unilateral and bilateral outcomes. However, further research is warranted to better understand the impact of that factor in a larger number of subjects with long-term hearing impairment of greater than 30 years. Better contralateral hearing was associated with poorer unilateral word scores with the implanted ear alone, but better absolute bilateral speech recognition. As a result, it is clear that different models would need to be developed to predict unilateral and bilateral postimplantation scores.11 page(s