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1.
New Phytol ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39224928

ABSTRACT

Effector secretion is crucial for root endophytes to establish and protect their ecological niche. We used time-resolved transcriptomics to monitor effector gene expression dynamics in two closely related Sebacinales, Serendipita indica and Serendipita vermifera, during symbiosis with three plant species, competition with the phytopathogenic fungus Bipolaris sorokiniana, and cooperation with root-associated bacteria. We observed increased effector gene expression in response to biotic interactions, particularly with plants, indicating their importance in host colonization. Some effectors responded to both plants and microbes, suggesting dual roles in intermicrobial competition and plant-microbe interactions. A subset of putative antimicrobial effectors, including a GH18-CBM5 chitinase, was induced exclusively by microbes. Functional analyses of this chitinase revealed its antimicrobial and plant-protective properties. We conclude that dynamic effector gene expression underpins the ability of Sebacinales to thrive in diverse ecological niches with a single fungal chitinase contributing substantially to niche defense.

2.
Nat Microbiol ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39209985

ABSTRACT

Fungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products.

3.
J Clin Med ; 13(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39200930

ABSTRACT

Introduction: This study evaluated the efficacy and safety of ultrasound-guided high-intensity focused ultrasound (HIFU) in treating symptomatic uterine fibroids and adenomyosis. Methods: HIFU treatments performed in premenopausal women with symptomatic uterine fibroids and adenomyosis were analyzed retrospectively. Lesion volume reduction, change in symptoms of menstrual pain, and quality of life were examined. Major and minor complications, together with re-intervention rates, were evaluated. Results: Eighty-one HIFU treatments were performed in seventy-nine premenopausal women. The follow-up period was up to 95 months. A total of 65 women underwent treatment for uterine fibroids and 14 were treated for adenomyosis. For patients with uterine fibroids, the baseline fibroid volume median was 190.1 cm3 (18.5-1729.4 cm3). Fibroid volume was reduced by 50.1% (-26.2-97.8, p < 0.0001) at 6 months and 66.9% (-33.7-98.3, p < 0.0001) at 12 months after treatment. The modified Uterine Fibroid Symptom and Quality of Life (UFS-QOL) scores had decreased by 43.5% (0-62.5%, p < 0.0001) at 6 months and 50% (0-73%, p < 0.0001) at 12 months after treatment. In the adenomyosis arm, the median baseline uterine volume was 97.7 cm3 (43.7-367.4 m3). Uterine volume was reduced by 19.6% (range: 1.2-42.0, p = 0.28) at 6 months and 41.9% (18.9-69.2, p = 0.04) at 12 months after treatment. UFS-QOL scores were reduced by 38.1% (6-66.7%, p < 0.0001) at 6 months and 40% (0-70%, p < 0.0001) at 12s month after treatment. Fourteen (21.5%) patients with uterine fibroid and five (35.7%) patients with adenomyosis required subsequent interventions. Conclusions: HIFU provides symptomatic relief to most patients with uterine fibroids and adenomyosis. It is a promising uterus-sparing treatment for patients with these conditions.

4.
Microbiol Resour Announc ; 13(8): e0014124, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-38967461

ABSTRACT

Papiliotrema laurentii 5307AH was isolated from an aircraft polymer-coated surface. The genome size is 19,510,785 bp with a G + C content of 56%. The genome harbors genes encoding oxygenases, cutinases, lipases, and enzymes for styrene degradation, all of which could play a critical role in survival on xenobiotic surfaces.

5.
Fungal Genet Biol ; 173: 103913, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39004162

ABSTRACT

Schizophyllum commune is a mushroom-forming fungus notable for its distinctive fruiting bodies with split gills. It is used as a model organism to study mushroom development, lignocellulose degradation and mating type loci. It is a hypervariable species with considerable genetic and phenotypic diversity between the strains. In this study, we systematically phenotyped 16 dikaryotic strains for aspects of mushroom development and 18 monokaryotic strains for lignocellulose degradation. There was considerable heterogeneity among the strains regarding these phenotypes. The majority of the strains developed mushrooms with varying morphologies, although some strains only grew vegetatively under the tested conditions. Growth on various carbon sources showed strain-specific profiles. The genomes of seven monokaryotic strains were sequenced and analyzed together with six previously published genome sequences. Moreover, the related species Schizophyllum fasciatum was sequenced. Although there was considerable genetic variation between the genome assemblies, the genes related to mushroom formation and lignocellulose degradation were well conserved. These sequenced genomes, in combination with the high phenotypic diversity, will provide a solid basis for functional genomics analyses of the strains of S. commune.


Subject(s)
Genetic Variation , Genome, Fungal , Genotype , Lignin , Phenotype , Schizophyllum , Schizophyllum/genetics , Schizophyllum/growth & development , Schizophyllum/classification , Lignin/metabolism , Genome, Fungal/genetics , Phylogeny , Agaricales/genetics , Agaricales/growth & development , Agaricales/classification , Sequence Analysis, DNA
6.
Nat Commun ; 15(1): 6066, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39025853

ABSTRACT

DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.


Subject(s)
Adenine , DNA Methylation , Gene Expression Regulation, Fungal , Mucorales , Adenine/metabolism , Mucorales/genetics , Mucorales/metabolism , Epigenesis, Genetic , Fungal Proteins/genetics , Fungal Proteins/metabolism , Phylogeny , Evolution, Molecular , Methyltransferases/metabolism , Methyltransferases/genetics , DNA, Fungal/genetics , DNA, Fungal/metabolism , Mutation
7.
JACC Adv ; 3(3): 100839, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38938839

ABSTRACT

Background: Augmented reality (AR) guidance holds potential to improve transcatheter interventions by enabling visualization of and interaction with patient-specific 3-dimensional virtual content. Positioning of cerebral embolic protection devices (CEP) during transcatheter aortic valve replacement (TAVR) increases patient exposure to radiation and iodinated contrast, and increases procedure time. AR may enhance procedural guidance and facilitate a safer intervention. Objectives: The purpose of this study was to develop and test a novel AR guidance system with a custom user interface that displays virtual, patient-specific 3-dimensional anatomic models, and assess its intraprocedural impact during CEP placement in TAVR. Methods: Patients undergoing CEP during TAVR were prospectively enrolled and assigned to either AR guidance or control groups. Primary endpoints were contrast volume used prior to filter placement, times to filter placement, and fluoroscopy time. Postprocedure questionnaires were administered to assess intraprocedural physician experience with AR guidance. Results: A total of 24 patients presenting for TAVR were enrolled in the study (12 with AR guidance and 12 controls). AR guidance eliminated the need for aortic arch angiograms prior to device placement thus reducing contrast volume (0 mL vs 15 mL, P < 0.0001). There was no significant difference in the time required for filter placement or fluoroscopy time. Postprocedure questionnaires indicated that AR guidance increased confidence in wiring of the aortic arch and facilitated easier device placement. Conclusions: We developed a novel AR guidance system that eliminated the need for additional intraprocedural angiograms prior to device placement without any significant difference in time to intervention and offered a subjective improvement in performance of the intervention.

8.
Front Bioeng Biotechnol ; 12: 1356551, 2024.
Article in English | MEDLINE | ID: mdl-38638323

ABSTRACT

The Lipomyces clade contains oleaginous yeast species with advantageous metabolic features for biochemical and biofuel production. Limited knowledge about the metabolic networks of the species and limited tools for genetic engineering have led to a relatively small amount of research on the microbes. Here, a genome-scale metabolic model (GSM) of Lipomyces starkeyi NRRL Y-11557 was built using orthologous protein mappings to model yeast species. Phenotypic growth assays were used to validate the GSM (66% accuracy) and indicated that NRRL Y-11557 utilized diverse carbohydrates but had more limited catabolism of organic acids. The final GSM contained 2,193 reactions, 1,909 metabolites, and 996 genes and was thus named iLst996. The model contained 96 of the annotated carbohydrate-active enzymes. iLst996 predicted a flux distribution in line with oleaginous yeast measurements and was utilized to predict theoretical lipid yields. Twenty-five other yeasts in the Lipomyces clade were then genome sequenced and annotated. Sixteen of the Lipomyces species had orthologs for more than 97% of the iLst996 genes, demonstrating the usefulness of iLst996 as a broad GSM for Lipomyces metabolism. Pathways that diverged from iLst996 mainly revolved around alternate carbon metabolism, with ortholog groups excluding NRRL Y-11557 annotated to be involved in transport, glycerolipid, and starch metabolism, among others. Overall, this study provides a useful modeling tool and data for analyzing and understanding Lipomyces species metabolism and will assist further engineering efforts in Lipomyces.

9.
Appl Environ Microbiol ; 90(5): e0169423, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38624219

ABSTRACT

Given the multitude of extracellular enzymes at their disposal, many of which are designed to degrade nature's polymers (lignin, cutin, cellulose, etc.), fungi are adept at targeting synthetic polyesters with similar chemical composition. Microbial-influenced deterioration of xenobiotic polymeric surfaces is an area of interest for material scientists as these are important for the conservation of the underlying structural materials. Here, we describe the isolation and characterization of the Papiliotrema laurentii 5307AH (P. laurentii) cutinase, Plcut1. P. laurentii is basidiomycete yeast with the ability to disperse Impranil-DLN (Impranil), a colloidal polyester polyurethane, in agar plates. To test whether the fungal factor involved in this clearing was a secreted enzyme, we screened the ability of P. laurentii culture supernatants to disperse Impranil. Using size exclusion chromatography (SEC), we isolated fractions that contained Impranil-clearing activity. These fractions harbored a single ~22 kD band, which was excised and subjected to peptide sequencing. Homology searches using the peptide sequences identified, revealed that the protein Papla1 543643 (Plcut1) displays similarities to serine esterase and cutinase family of proteins. Biochemical assays using recombinant Plcut1 confirmed that this enzyme has the capability to hydrolyze Impranil, soluble esterase substrates, and apple cutin. Finally, we confirmed the presence of the Plcut1 in culture supernatants using a custom antibody that specifically recognizes this protein. The work shown here supports a major role for the Plcut1 in the fungal degradation of natural polyesters and xenobiotic polymer surfaces.IMPORTANCEFungi play a vital role in the execution of a broad range of biological processes that drive ecosystem function through production of a diverse arsenal of enzymes. However, the universal reactivity of these enzymes is a current problem for the built environment and the undesired degradation of polymeric materials in protective coatings. Here, we report the identification and characterization of a hydrolase from Papiliotrema laurentii 5307AH, an aircraft-derived fungal isolate found colonizing a biodeteriorated polymer-coated surface. We show that P. laurentii secretes a cutinase capable of hydrolyzing soluble esters as well as ester-based compounds forming solid surface coatings. These findings indicate that this fungus plays a significant role in biodeterioration through the production of a cutinase adept at degrading ester-based polymers, some of which form the backbone of protective surface coatings. The work shown here provides insights into the mechanisms employed by fungi to degrade xenobiotic polymers.


Subject(s)
Carboxylic Ester Hydrolases , Fungal Proteins , Polyesters , Recombinant Proteins , Carboxylic Ester Hydrolases/metabolism , Carboxylic Ester Hydrolases/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Polyesters/metabolism , Hydrolysis
10.
AJOG Glob Rep ; 4(1): 100315, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38362048

ABSTRACT

BACKGROUND: Unrecognized diabetes mellitus during pregnancy could pose serious maternal and neonatal complications. A hemoglobin A1c level of ≥6.5% was used to diagnose both diabetes mellitus in nonpregnant individuals and diabetes in pregnancy. As the hemoglobin A1c level could be influenced by maternal physiological changes, the optimal cutoff in early pregnancy to detect women with diabetes in pregnancy and associated complications remains unclear. OBJECTIVE: This study aimed to evaluate the diagnostic performance of various hemoglobin A1c levels and the optimal hemoglobin A1c cutoff to identify mothers with diabetes in pregnancy diagnosed by the gold standard 75 g oral glucose tolerance test before 24 weeks of gestation. In addition, the pregnancy and neonatal outcomes were compared using the optimal hemoglobin A1c cutoff. STUDY DESIGN: A retrospective cohort study was conducted between 2004 and 2019. Women with at least 1 risk factor of gestational diabetes mellitus received an oral glucose tolerance test before 24 weeks of gestation. Terminology of hyperglycemia first detected during pregnancy by oral glucose tolerance test was classified as either diabetes in pregnancy or gestational diabetes mellitus following the World Health Organization's recommendation. Women who met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus (ie, before 24 weeks of gestation) and had a paired hemoglobin A1c measurement within 4 weeks of their early oral glucose tolerance test were studied. Sensitivity, specificity, and positive and negative predictive values at various hemoglobin A1c cutoffs were calculated for the detection of diabetes in pregnancy. The optimal hemoglobin A1c level was identified from the constructed receiver operating characteristic curves. Multivariate binary logistic regression analyses were performed to calculate the unadjusted and adjusted odds ratios for pregnancy complications. RESULTS: There were 63,111 deliveries, and 22,949 women underwent an oral glucose tolerance test before 24 weeks of gestation. A total of 157 and 3210 women met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus using an oral glucose tolerance test, respectively. Only 346 participants had a paired hemoglobin A1c and oral glucose tolerance test measurement (82 cases with diabetes in pregnancy and 264 cases with early-onset gestational diabetes mellitus). The receiver operating characteristic curve identified an optimal hemoglobin A1c cutoff of 5.7% to diagnose diabetes in pregnancy, with a sensitivity of 64.6%, specificity of 81.1%, positive predictive value of 51.5%, and negative predictive value of 88.1%. A hemoglobin A1c cutoff of either 5.9% or 6.5% could miss 47.6% or 73.2% of women with diabetes in pregnancy. In multivariate logistic regression analysis, a hemoglobin A1c level of ≥5.7% increased the risk of maternal insulin use (adjusted odds ratio, 6.69; 95% confidence interval, 3.44-12.99), macrosomia (adjusted odds ratio, 7.43; 95% confidence interval, 1.90-29.00), and shoulder dystocia (adjusted odds ratio, 6.56; 95% confidence interval, 1.161-37.03). CONCLUSION: The optimal hemoglobin A1c cutoff to detect diabetes in pregnancy diagnosed using an oral glucose tolerance test before 24 weeks of gestation was 5.7%, but this cutoff could not reliably identify diabetes in pregnancy owing to the low sensitivity. However, an early hemoglobin A1c level of ≥5.7% indicated increased risks of pregnancy and neonatal complications.

11.
JACC Cardiovasc Interv ; 17(4): 491-501, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38340105

ABSTRACT

BACKGROUND: Intravascular ultrasound (IVUS) studies show that one-quarter of left anterior descending (LAD) arteries have a myocardial bridge. An MB may be associated with stent failure when the stent extends into the MB. OBJECTIVES: The aim of this study was to investigate: 1) the association between an MB and chronic total occlusion (CTO) in any LAD lesions; and 2) the association between an MB and subsequent clinical outcomes after percutaneous coronary intervention in LAD CTOs. METHODS: A total of 3,342 LAD lesions with IVUS-guided percutaneous coronary intervention (280 CTO and 3,062 non-CTO lesions) were included. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischemic-driven target lesion revascularization). RESULTS: An MB by IVUS was significantly more prevalent in LAD CTOs than LAD non-CTOs (40.4% [113/280] vs 25.8% [789/3,062]; P < 0.0001). The discrepancy in CTO length between angiography and IVUS was greater in 113 LAD CTOs with an MB than 167 LAD CTOs without an MB (6.0 [Q1, Q3: 0.1, 12.2] mm vs 0.2 [Q1, Q3: -1.4, 8.4] mm; P < 0.0001). Overall, 48.7% (55/113) of LAD CTOs had a stent that extended into an MB after which target lesion failure was significantly higher compared to a stent that did not extend into an MB (26.3% vs 0%; P = 0.0004) or compared to an LAD CTO without an MB (26.3% vs 9.6%; P = 0.02). CONCLUSIONS: An MB was more common in LAD CTO than non-CTO LAD lesions. If present, approximately one-half of LAD CTOs had a stent extending into an MB that, in turn, was associated with worse outcomes.


Subject(s)
Coronary Occlusion , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/therapy , Treatment Outcome , Percutaneous Coronary Intervention/adverse effects , Coronary Angiography , Chronic Disease
12.
EuroIntervention ; 20(3): e207-e215, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38343369

ABSTRACT

BACKGROUND: Outcomes after percutaneous coronary intervention (PCI) for de novo ostial right coronary artery (RCA) lesions are poor. AIMS: We used intravascular ultrasound (IVUS) to clarify the morphological patterns of de novo ostial RCA lesions and their associated clinical outcome. METHODS: Among 5,102 RCA IVUS studies, 170 de novo ostial RCA stenoses (within 3 mm from the aorto-ostium) were identified. These were classified as 1) isolated ostial lesions (no disease extending beyond 10 mm from the ostium and without a calcified nodule [CN]); 2) ostial CN, typically with diffuse disease (disease extending beyond 10 mm); and 3) ostial lesions with diffuse disease but without a CN. The primary outcome was target lesion failure (TLF: cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischaemia-driven target lesion revascularisation). RESULTS: The prevalence of an isolated ostial lesion was 11.8% (n=20), 47.6% (n=81) were ostial CN, and 40.6% (n=69) were ostial lesions with diffuse disease. Compared to ostial lesions with diffuse disease, isolated lesions were more common in women (75.0% vs 42.0%; p=0.01), and CN were associated with older age (median [first, third quartile] 76 [70, 83] vs 69 [63, 81] years old; p=0.002). The Kaplan-Meier rate of TLF at 2 years was significantly higher in patients with CN (21.6%) compared to diffuse lesions (8.2%) (p=0.04), and patients with isolated lesions had no events. A multivariable Cox proportional hazard model revealed that CN were significantly associated with TLF (hazard ratio 6.63, 95% confidence interval: 1.28-34.3; p=0.02). CONCLUSIONS: Ostial RCA lesions have specific morphologies - detectable by IVUS - that may be associated with long-term clinical outcomes.


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Female , Aged, 80 and over , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/etiology , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Risk Factors , Coronary Angiography
13.
Catheter Cardiovasc Interv ; 103(2): 367-375, 2024 02.
Article in English | MEDLINE | ID: mdl-37890014

ABSTRACT

AIMS: Characterize the impact of residual tricuspid regurgitation (TR) on right ventricle (RV) remodeling and clinical outcomes after transcatheter tricuspid valve intervention. METHODS: We performed a single-center retrospective analysis of transcatheter tricuspid valve repair (TTVr) or replacement (TTVR) patients. The primary outcomes were longitudinal tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure (PASP), and RV dimensions (RVd). We used multivariable linear mixed models to evaluate association with replacement versus repair and degree of TR reduction with changes in these echo measures over time. Multivariable Cox regression was used to identify associations between changes in these echo measures and a composite clinical outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention. RESULTS: We included a total of 61 patients; mean age was 77.5 ± 11.7 and 62% were female. TTVR was performed in 25 (41%) and TTVr in 36 (59%). Initially, 72% (n = 44) had ≤ severe TR and 28% (n = 17) had massive or torrential TR. The median number of follow up echos was 2: time to 1st follow-up was 50 days (interquartile range [IQR]: 20, 91) and last follow-up was 147 (IQR: 90, 327). Median TR reduction was 1 (IQR: 0, 2) versus 4 (IQR: 3, 6) grades in TTVr versus TTVR (p < 0.0001). In linear mixed modeling, TTVR was associated with decline in TAPSE and PASP, and TR reduction was associated with decreased RVd. In multivariable Cox regression, greater RVd was associated with the clinical outcome (hazard ratio: 9.27, 95% confidence interval: 1.23-69.88, p = 0.03). CONCLUSION: Greater TR reduction is achieved by TTVR versus TTVr, which is in turn associated with RV reverse remodeling. RV dimension in follow-up is associated with increased risk of a composite outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention.


Subject(s)
Heart Failure , Tricuspid Valve Insufficiency , Humans , Female , Aged , Aged, 80 and over , Male , Tricuspid Valve/diagnostic imaging , Tricuspid Valve/surgery , Retrospective Studies , Ventricular Remodeling , Treatment Outcome , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/surgery , Tricuspid Valve Insufficiency/complications , Heart Failure/diagnostic imaging , Heart Failure/therapy
14.
Int J Mol Sci ; 24(23)2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38069150

ABSTRACT

Pleurotus ostreatus is a white-rot fungus that can degrade lignin in a preferential manner using a variety of extracellular enzymes, including manganese and versatile peroxidases (encoded by the vp1-3 and mnp1-6 genes, respectively). This fungus also secretes a family of structurally related small secreted proteins (SSPs) encoded by the ssp1-6 genes. Using RNA sequencing (RNA-seq), we determined that ssp4 and ssp6 are the predominant members of this gene family that were expressed by P. ostreatus during the first three weeks of growth on wheat straw. Downregulation of ssp4 in a strain harboring an ssp RNAi construct (KDssp1) was then confirmed, which, along with an increase in ssp6 transcript levels, coincided with reduced lignin degradation and the downregulation of vp2 and mnp1. In contrast, we observed an increase in the expression of genes related to pectin and side-chain hemicellulose degradation, which was accompanied by an increase in extracellular pectin-degrading capacity. Genome-wide comparisons between the KDssp1 and the wild-type strains demonstrated that ssp silencing conferred accumulated changes in gene expression at the advanced cultivation stages in an adaptive rather than an inductive mode of transcriptional response. Based on co-expression networking, crucial gene modules were identified and linked to the ssp knockdown genotype at different cultivation times. Based on these data, as well as previous studies, we propose that P. ostreatus SSPs have potential roles in modulating the lignocellulolytic and pectinolytic systems, as well as a variety of fundamental biological processes related to fungal growth and development.


Subject(s)
Lignin , Pleurotus , Lignin/metabolism , Pleurotus/metabolism , Peroxidases/genetics , Peroxidases/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Pectins/metabolism
15.
Microbiol Resour Announc ; 12(12): e0043523, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-37982613

ABSTRACT

Yarrowia lipolytica is an oleaginous yeast that produces high titers of fatty acid-derived biofuels and biochemicals. It can grow on hydrophobic carbon sources and lignocellulosic hydrolysates. The genome sequence of Y. lipolytica NRRL Y-64008 is reported to aid in its development as a biotechnological chassis for producing biofuels and bioproducts.

16.
Sci Adv ; 9(44): eadi4777, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37922358

ABSTRACT

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.


Subject(s)
Pre-Eclampsia , Pregnancy , Female , Mice , Humans , Animals , Pre-Eclampsia/therapy , Pre-Eclampsia/metabolism , Trophoblasts/metabolism , Adrenomedullin/metabolism , Placenta/metabolism , Cell Differentiation
17.
Front Public Health ; 11: 1212583, 2023.
Article in English | MEDLINE | ID: mdl-37876714

ABSTRACT

Current guidelines for evaluating the cost-effectiveness of health interventions commonly recommend the use of a payer and/or a societal perspective. This raises the concern that the resulting reimbursement decision may overlook the full spectrum of impacts and equity considerations. In this paper, we argue that a potential solution is to supplement a societal- or payer-perspective economic evaluation with an additional evaluation accounting for exclusively the patient perspective. We present five categories of health interventions for which a patient-perspective analysis may be informative including those (1) that cross the definitional boundary between drugs and non-drug technologies; (2) affect patient adherence to protocol; (3) represent revolutionary treatments for genetic disorders; (4) with an incremental cost-effectiveness ratio involving slightly less effective, but substantially less costly, than the current standard; and (5) have been previously approved for funding but now being targeted for potential delisting or disinvestment. Real-world examples are discussed in detail. Lived experience individuals were invited to provide vignettes. Discussions are provided regarding how to incorporate patient inputs to improve patient-centered decision-making.


Subject(s)
Patients , Humans , Cost-Benefit Analysis
18.
Microbiol Resour Announc ; 12(11): e0042623, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37906027

ABSTRACT

Lipomyces tetrasporous is an oleaginous yeast that can utilize a variety of plant-based sugars. It accumulates lipids during growth on lignocellulosic biomass hydrolysates. We present the annotated genome sequence of L. tetrasporous NRRL Y-64009 to aid in its development as a platform organism for producing lipids and lipid-based bioproducts.

20.
Mol Phylogenet Evol ; 189: 107938, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37820761

ABSTRACT

The order Sordariales is taxonomically diverse, and harbours many species with different lifestyles and large economic importance. Despite its importance, a robust genome-scale phylogeny, and associated comparative genomic analysis of the order is lacking. In this study, we examined whole-genome data from 99 Sordariales, including 52 newly sequenced genomes, and seven outgroup taxa. We inferred a comprehensive phylogeny that resolved several contentious relationships amongst families in the order, and cleared-up intrafamily relationships within the Podosporaceae. Extensive comparative genomics showed that genomes from the three largest families in the dataset (Chaetomiaceae, Podosporaceae and Sordariaceae) differ greatly in GC content, genome size, gene number, repeat percentage, evolutionary rate, and genome content affected by repeat-induced point mutations (RIP). All genomic traits showed phylogenetic signal, and ancestral state reconstruction revealed that the variation of the properties stems primarily from within-family evolution. Together, the results provide a thorough framework for understanding genome evolution in this important group of fungi.


Subject(s)
Genomics , Sordariales , Humans , Phylogeny , Genomics/methods , Genome , Sordariales/genetics , Base Sequence , Evolution, Molecular
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