Nature. 2024 Aug 14. doi: 10.1038/s41586-024-07832-z. Online ahead of print.

ABSTRACT

Guanidine is a chemically stable nitrogen compound that is excreted in human urine and is widely used in manufacturing of plastics, as a flame retardant and as a component of propellants, and is well known as a protein denaturant in biochemistry1-3. Guanidine occurs widely in nature and is used by several microorganisms as a nitrogen source, but microorganisms growing on guanidine as the only substrate have not yet been identified. Here we show that the complete ammonia oxidizer (comammox) Nitrospira inopinata and probably most other comammox microorganisms can grow on guanidine as the sole source of energy, reductant and nitrogen. Proteomics, enzyme kinetics and the crystal structure of a N. inopinata guanidinase homologue demonstrated that it is a bona fide guanidinase. Incubation experiments with comammox-containing agricultural soil and wastewater treatment plant microbiomes suggested that guanidine serves as substrate for nitrification in the environment. The identification of guanidine as a growth substrate for comammox shows an unexpected niche of these globally important nitrifiers and offers opportunities for their isolation.

PMID:39143220 | DOI:10.1038/s41586-024-07832-z

Sci Rep. 2024 Aug 14;14(1):18866. doi: 10.1038/s41598-024-69685-w.

ABSTRACT

Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we used metatranscriptomics to investigate how IMMPs with different amounts of α - (1 → 6) glycosidic linkages affected microbial function during incubation with human fecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of α - (1 → 6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes.

PMID:39143192 | DOI:10.1038/s41598-024-69685-w

NPJ Syst Biol Appl. 2024 Aug 14;10(1):88. doi: 10.1038/s41540-024-00415-8.

ABSTRACT

We present a study where predictive mechanistic modeling is combined with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) immunotherapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models of key mechanisms underlying ICI therapy that may not be directly measurable in the clinic and easily measurable quantities or patient characteristics that are not always readily incorporated into predictive mechanistic models. A deep learning time-to-event predictive model trained on a hybrid mechanistic + clinical data set from 93 patients achieved higher per-patient predictive accuracy based on event-time concordance, Brier score, and negative binomial log-likelihood-based criteria than when trained on only mechanistic model-derived values or only clinical data. Feature importance analysis revealed that both clinical and model-derived parameters play prominent roles in increasing prediction accuracy, further supporting the advantage of our hybrid approach.

PMID:39143136 | DOI:10.1038/s41540-024-00415-8

Cell Res. 2024 Aug 14. doi: 10.1038/s41422-024-01014-2. Online ahead of print.

ABSTRACT

Abiotic D-proteins that selectively bind to natural L-proteins have gained significant biotechnological interest. However, the underlying structural principles governing such heterochiral protein-protein interactions remain largely unknown. In this study, we present the de novo design of D-proteins consisting of 50-65 residues, aiming to target specific surface regions of L-proteins or L-peptides. Our designer D-protein binders exhibit nanomolar affinity toward an artificial L-peptide, as well as two naturally occurring proteins of therapeutic significance: the D5 domain of human tropomyosin receptor kinase A (TrkA) and human interleukin-6 (IL-6). Notably, these D-protein binders demonstrate high enantiomeric specificity and target specificity. In cell-based experiments, designer D-protein binders effectively inhibited the downstream signaling of TrkA and IL-6 with high potency. Moreover, these binders exhibited remarkable thermal stability and resistance to protease degradation. Crystal structure of the designed heterochiral D-protein-L-peptide complex, obtained at a resolution of 2.0 Å, closely resembled the design model, indicating that the computational method employed is highly accurate. Furthermore, the crystal structure provides valuable information regarding the interactions between helical L-peptides and D-proteins, particularly elucidating a novel mode of heterochiral helix-helix interactions. Leveraging the design of D-proteins specifically targeting L-peptides or L-proteins opens up avenues for systematic exploration of the mirror-image protein universe, paving the way for a diverse range of applications.

PMID:39143121 | DOI:10.1038/s41422-024-01014-2

Nat Commun. 2024 Aug 14;15(1):7006. doi: 10.1038/s41467-024-51381-y.

ABSTRACT

The Na+-Cl- cotransporter (NCC) drives salt reabsorption in the kidney and plays a decisive role in balancing electrolytes and blood pressure. Thiazide and thiazide-like diuretics inhibit NCC-mediated renal salt retention and have been cornerstones for treating hypertension and edema since the 1950s. Here we determine NCC co-structures individually complexed with the thiazide drug hydrochlorothiazide, and two thiazide-like drugs chlorthalidone and indapamide, revealing that they fit into an orthosteric site and occlude the NCC ion translocation pathway. Aberrant NCC activation by the WNKs-SPAK kinase cascade underlies Familial Hyperkalemic Hypertension, but it remains unknown whether/how phosphorylation transforms the NCC structure to accelerate ion translocation. We show that an intracellular amino-terminal motif of NCC, once phosphorylated, associates with the carboxyl-terminal domain, and together, they interact with the transmembrane domain. These interactions suggest a phosphorylation-dependent allosteric network that directly influences NCC ion translocation.

PMID:39143061 | DOI:10.1038/s41467-024-51381-y

J Infect. 2024 Aug 12:106243. doi: 10.1016/j.jinf.2024.106243. Online ahead of print.

ABSTRACT

OBJECTIVES: High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood.

METHODS: We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) were identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified.

RESULTS: Stool samples were provided by 164 participants (median age: 88 years, IQR 81-93; 72% female). Sixty-one percent (n=100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1-52), most commonly a penicillin (n=55, 33.5%), cephalosporin (n=53, 32.3%), diaminopyrimidine (trimethoprim) (n=36, 22%), or tetracycline (doxycycline) (n=21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q<0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q<0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30-100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q<0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q<0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n=162, median: 3, IQR: 2-4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations.

CONCLUSIONS: The gut microbiome of aged care residents is a major reservoir of antibiotic resistance. As a critical antibiotic in medical practice, a comprehensive understanding of the impact of doxycycline exposure on the gut resistome is paramount for informed antibiotic use, particularly in an evolving landscape of prophylactic applications. Near-universal asymptomatic carriage of clinically critical resistance determinants is highly concerning and reinforces the urgent need for improved management of antibiotic use in long-term aged care.

FUNDING: Medical Research Future Fund, Australia.

PMID:39142392 | DOI:10.1016/j.jinf.2024.106243

Cell Syst. 2024 Aug 7:S2405-4712(24)00202-3. doi: 10.1016/j.cels.2024.07.003. Online ahead of print.

ABSTRACT

Functional magnetic resonance imaging (fMRI) provides insights into cognitive processes with significant clinical potential. However, delays in brain region communication and dynamic variations are often overlooked in functional network studies. We demonstrate that networks extracted from fMRI cross-correlation matrices, considering time lags between signals, show remarkable reliability when focusing on statistical distributions of network properties. This reveals a robust brain functional connectivity pattern, featuring a sparse backbone of strong 0-lag correlations and weaker links capturing coordination at various time delays. This dynamic yet stable network architecture is consistent across rats, marmosets, and humans, as well as in electroencephalogram (EEG) data, indicating potential universality in brain dynamics. Second-order properties of the dynamic functional network reveal a remarkably stable hierarchy of functional correlations in both group-level comparisons and test-retest analyses. Validation using alcohol use disorder fMRI data uncovers broader shifts in network properties than previously reported, demonstrating the potential of this method for identifying disease biomarkers.

PMID:39142285 | DOI:10.1016/j.cels.2024.07.003

Mol Cell. 2024 Aug 6:S1097-2765(24)00616-6. doi: 10.1016/j.molcel.2024.07.018. Online ahead of print.

ABSTRACT

G-quadruplexes (G4s) form throughout the genome and influence important cellular processes. Their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected role for the double-stranded DNA (dsDNA) translocase helicase-like transcription factor (HLTF) in responding to G4s. We show that HLTF, which is enriched at G4s in the human genome, can directly unfold G4s in vitro and uses this ATP-dependent translocase function to suppress G4 accumulation throughout the cell cycle. Additionally, MSH2 (a component of MutS heterodimers that bind G4s) and HLTF act synergistically to suppress G4 accumulation, restrict alternative lengthening of telomeres, and promote resistance to G4-stabilizing drugs. In a discrete but complementary role, HLTF restrains DNA synthesis when G4s are stabilized by suppressing primase-polymerase (PrimPol)-dependent repriming. Together, the distinct roles of HLTF in the G4 response prevent DNA damage and potentially mutagenic replication to safeguard genome stability.

PMID:39142279 | DOI:10.1016/j.molcel.2024.07.018

Sci Adv. 2024 Aug 16;10(33):eadn3316. doi: 10.1126/sciadv.adn3316. Epub 2024 Aug 14.

ABSTRACT

Genetic variations are instrumental for unraveling phage evolution and deciphering their functional implications. Here, we explore the underlying fine-scale genetic variations in the gut phageome, especially structural variations (SVs). By using virome-enriched long-read metagenomic sequencing across 91 individuals, we identified a total of 14,438 nonredundant phage SVs and revealed their prevalence within the human gut phageome. These SVs are mainly enriched in genes involved in recombination, DNA methylation, and antibiotic resistance. Notably, a substantial fraction of phage SV sequences share close homology with bacterial fragments, with most SVs enriched for horizontal gene transfer (HGT) mechanism. Further investigations showed that these SV sequences were genetic exchanged between specific phage-bacteria pairs, particularly between phages and their respective bacterial hosts. Temperate phages exhibit a higher frequency of genetic exchange with bacterial chromosomes and then virulent phages. Collectively, our findings provide insights into the genetic landscape of the human gut phageome.

PMID:39141729 | DOI:10.1126/sciadv.adn3316

Plant Cell. 2024 Aug 14:koae231. doi: 10.1093/plcell/koae231. Online ahead of print.

NO ABSTRACT

PMID:39141596 | DOI:10.1093/plcell/koae231

Methods Mol Biol. 2024;2846:169-179. doi: 10.1007/978-1-0716-4071-5_11.

ABSTRACT

Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) allows for the identification of genomic targeting of DNA-binding proteins. Cleavage Under Targets and Release Using Nuclease (CUT&RUN) modifies this process by including a nuclease to digest DNA around a protein of interest. The result is a higher signal-to-noise ratio and decreased required starting material. This allows for high-fidelity sequence identification from as few as 500 cells, enabling chromatin profiling of precious tissue samples or primary cell types, as well as less abundant chromatin-binding proteins: all at significantly increased throughput.

PMID:39141236 | DOI:10.1007/978-1-0716-4071-5_11

Plant Physiol. 2024 Aug 14:kiae419. doi: 10.1093/plphys/kiae419. Online ahead of print.

ABSTRACT

Oriented cell divisions establish plant tissue and organ patterning and produce different cell types; this is particularly true of the highly organized Arabidopsis (Arabidopsis thaliana) root meristem. Mutant alleles of INFLORESCENCE AND ROOT APICES RECEPTOR KINASE (IRK) exhibit excess cell divisions in the root endodermis. IRK is a transmembrane receptor kinase that localizes to the outer polar domain of these cells, suggesting that directional signal perception is necessary to repress endodermal cell division. Here, a detailed examination revealed many of the excess endodermal divisions in irk have division planes that specifically skew towards the outer lateral side. Therefore, we termed them 'outward askew' divisions. Expression of an IRK truncation lacking the kinase domain retains polar localization and prevents outward askew divisions in irk; however, the roots exhibit excess periclinal endodermal divisions. Using cell identity markers, we show that the daughters of outward askew divisions transition from endodermal to cortical identity similar to those of periclinal divisions. These results extend the requirement for IRK beyond repression of cell division activity to include cell division plane positioning. Based on its polarity, we propose that IRK at the outer lateral endodermal cell face participates in division plane positioning to ensure normal root ground tissue patterning.

PMID:39140752 | DOI:10.1093/plphys/kiae419

Alzheimers Dement. 2024 Aug 14. doi: 10.1002/alz.14095. Online ahead of print.

ABSTRACT

INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.

METHODS: Here, we integrated [18F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis.

RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG-PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak-t(223) = 4.86, P value < 0.001) and zinc-finger-related regulatory units (peak-t(223) = 3.90, P value < 0.001).

DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity-associated genes and zinc-finger-related regulatory units are highly associated with brain metabolic changes in AD.

HIGHLIGHTS: We conducted an integrated analysis of system-based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) at the voxel level in Alzheimer's disease (AD). The biological process of serine/threonine kinase activity was the most associated with [18F]FDG-PET in the AD brain. Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG-PET. Zinc-finger transcription factor targets were associated with AD brain [18F]FDG-PET metabolism.

PMID:39140361 | DOI:10.1002/alz.14095

JMIR Public Health Surveill. 2024 Aug 12;10:e50244. doi: 10.2196/50244.

ABSTRACT

BACKGROUND: The evidence on the association of fine particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) with pulmonary tuberculosis (PTB) retreatment is limited. There are no data on whether greenness exposure protects air pollution-related PTB retreatment in patients with prior PTB.

OBJECTIVE: In a population-based retrospective study, we aimed to investigate the influence of PM2.5 and residential greenness on the risk of PTB retreatment.

METHODS: A total of 26,482 patients with incident PTB, registered in a mandatory web-based reporting system between 2012 and 2019 in Zhengzhou, China, were included in the analysis. The exposure to PM2.5 was assessed based on the China High Air Pollutants dataset, and the level of greenness was estimated using the Normalized Difference Vegetation Index (NDVI) values. The associations of PTB retreatment with exposure to PM2.5 and greenness were evaluated, respectively, considering the local socioeconomic level indicated by the nighttime light index.

RESULTS: Among the 26,482 patients (mean age 46.86, SD 19.52 years) with a median follow-up time of 1523 days per patient, 1542 (5.82%) PTB retreatments were observed between 2012 and 2019. Exposure to PM2.5 was observed to be significantly associated with the increased risk of PTB retreatment in fully adjusted models with a hazard ratio of 1.97 (95% CI 1.34-2.83) per 10 μg/m3 increase in PM2.5. Patients living in the regions with relatively high quartiles of NDVI values had a 45% lower risk of PTB retreatment than those living in the regions with the lowest quartile for the 500 m buffers (hazard ratio 0.55, 95% CI 0.40-0.77). Such a protective effect of residential greenness was more pronounced among patients living in lower nighttime light areas. The strength of the association between PM2.5 exposure and the risk of PTB retreatment was attenuated by greenness. No significant association was observed between NDVI and the incidence of drug resistance.

CONCLUSIONS: Long-term exposure to PM2.5 might be a risk factor for PTB retreatment, while an increased level of residential greenness was found to be associated with reduced risks of PTB retreatment. Our results suggest strengthening the control of ambient air pollution and improving residential greenness may contribute to the reduction of PTB retreatment.

PMID:39140280 | DOI:10.2196/50244

Fungal Syst Evol. 2024 Jun;13:183-440. doi: 10.3114/fuse.2024.13.11. Epub 2024 Jun 28.

ABSTRACT

Novel species of fungi described in this study include those from various countries as follows: Australia, Baobabopsis sabindy in leaves of Eragrostis spartinoides, Cortinarius magentiguttatus among deep leaf litter, Laurobasidium azarandamiae from uredinium of Puccinia alyxiae on Alyxia buxifolia, Marasmius pseudoelegans on well-rotted twigs and litter in mixed wet sclerophyll and subtropical rainforest. Bolivia, Favolaschia luminosa on twigs of Byttneria hirsuta, Lecanora thorstenii on bark, in savannas with shrubs and trees. Brazil, Asterina costamaiae on leaves of Rourea bahiensis, Purimyces orchidacearum (incl. Purimyces gen. nov.) as root endophyte on Cattleya locatellii. Bulgaria, Monosporascus bulgaricus and Monosporascus europaeus isolated from surface-sterilised, asymptomatic roots of Microthlaspi perfoliatum. Finland, Inocybe undatolacera on a lawn, near Betula pendula. France, Inocybe querciphila in humus of mixed forest. Germany, Arrhenia oblongispora on bare soil attached to debris of herbaceous plants and grasses. Greece, Tuber aereum under Quercus coccifera and Acer sempervirens. India, Alfoldia lenyadriensis from the gut of a Platynotus sp. beetle, Fulvifomes subramanianii on living Albizzia amara, Inosperma pavithrum on soil, Phylloporia parvateya on living Lonicera sp., Tropicoporus maritimus on living Peltophorum pterocarpum. Indonesia, Elsinoe atypica on leaf of Eucalyptus pellita. Italy, Apiotrichum vineum from grape wine, Cuphopyllus praecox among grass. Madagascar, Pisolithus madagascariensis on soil under Intsia bijuga. Netherlands, Cytosporella calamagrostidis and Periconia calamagrostidicola on old leaves of Calamagrostis arenaria, Hyaloscypha caricicola on leaves of Carex sp., Neoniesslia phragmiticola (incl. Neoniesslia gen. nov.) on leaf sheaths of standing dead culms of Phragmites australis, Neptunomyces juncicola on culms of Juncus maritimus, Zenophaeosphaeria calamagrostidis (incl. Zenophaeosphaeria gen. nov.) on culms of Calamagrostis arenaria. Norway, Hausneria geniculata (incl. Hausneria gen. nov.) from a gallery of Dryocoetes alni on Alnus incana. Pakistan, Agrocybe auriolus on leaf litter of Eucalyptus camaldulensis, Rhodophana rubrodisca in nutrient-rich loamy soil with Morus alba. Poland, Cladosporium nubilum from hypersaline brine, Entomortierella ferrotolerans from soil at mines and postmining sites, Pseudopezicula epiphylla from sooty mould community on Quercus robur, Quixadomyces sanctacrucensis from resin of Pinus sylvestris, Szafranskia beskidensis (incl. Szafranskia gen. nov.) from resin of Abies alba. Portugal, Ascocoryne laurisilvae on degraded wood of Laurus nobilis, Hygrocybe madeirensis in laurel forests, Hygrocybula terracocta (incl. Hygrocybula gen. nov.) on mossy areas of laurel forests planted with Cryptomeria japonica. Republic of Kenya, Penicillium gorferi from a sterile chicken feather embedded in a soil sample. Slovakia, Cerinomyces tatrensis on bark of Pinus mugo, Metapochonia simonovicovae from soil. South Africa, Acremonium agapanthi on culms of Agapanthus praecox, Alfaria elegiae on culms of Elegia ebracteata, Beaucarneamyces stellenboschensis (incl. Beaucarneamyces gen. nov.) on dead leaves of Beaucarnea stricta, Gardeniomyces kirstenboschensis (incl. Gardeniomyces gen. nov.) rotting fruit of Gardenia thunbergia, Knufia dianellae on dead leaves of Dianella caerulea, Lomaantha quercina on twigs of Quercus suber. Melanina restionis on dead leaves of Restio duthieae, Microdochium buffelskloofinum on seeds of Eragrostis cf. racemosa, Thamnochortomyces kirstenboschensis (incl. Thamnochortomyces gen. nov.) on culms of Thamnochortus fraternus, Tubeufia hagahagana on leaves of Hypoxis angustifolia, Wingfieldomyces cypericola on dead leaves of Cyperus papyrus. Spain, Geastrum federeri in soil under Quercus suber and Q. canariensis, Geastrum nadalii in calcareous soil under Juniperus, Quercus, Cupressus, Pinus and Robinia, Hygrocybe garajonayensis in laurel forests, Inocybe cistophila on acidic soil under Cistus ladanifer, Inocybe sabuligena in a mixed Quercus ilex subsp. ballota/Juniperus thurifera open forest, Mycena calongei on mossy bark base of Juniperus oxycedrus, Rhodophana ulmaria on soil in Ulmus minor forest, Tuber arriacaense in soil under Populus pyramidalis, Volvariella latispora on grassy soils in a Quercus ilex ssp. rotundifolia stand. Sweden, Inocybe iota in alpine heath on calcareous soil. Thailand, Craterellus maerimensis and Craterellus sanbuakwaiensis on laterite and sandy soil, Helicocollum samlanense on scale insects, Leptosporella cassiae on dead twigs of Cassia fistula, Oxydothis coperniciae on dead leaf of Copernicia alba, Russula mukdahanensis on soil, Trechispora sangria on soil, Trechispora sanpatongensis on soil. Türkiye, Amanita corylophila in a plantation of Corylus avellana. Ukraine, Pararthrophiala adonis (incl. Pararthrophiala gen. nov.) on dead stems of Adonis vernalis. USA, Cladorrhinum carnegieae from Carnegiea gigantea, Dematipyriformia americana on swab from basement wall, Dothiora americana from outside air, Dwiroopa aeria from bedroom air, Lithohypha cladosporioides from hospital swab, Macroconia verruculosa on twig of Ilex montana, associated with black destroyed ascomycetous fungus and Biatora sp., Periconia floridana from outside air, Phytophthora fagacearum from necrotic leaves and shoots of Fagus grandifolia, Queenslandipenidiella californica on wood in crawlspace. Morphological and culture characteristics are supported by DNA barcodes. Citation: Crous PW, Jurjević Z, Balashov S, De la Peña-Lastra S, Mateos A, Pinruan U, Rigueiro-Rodríguez A, Osieck ER, Altés A, Czachura P, Esteve-Raventós F, Gunaseelan S, Kaliyaperumal M, Larsson E, Luangsa-ard JJ, Moreno G, Pancorbo F, Piątek M, Sommai S, Somrithipol S, Asif M, Delgado G, Flakus A, Illescas T, Kezo K, Khamsuntorn P, Kubátová A, Labuda R, Lavoise C, Lebel T, Lueangjaroenkit P, Maciá-Vicente JG, Paz A, Saba M, Shivas RG, Tan YP, Wingfield MJ, Aas T, Abramczyk B, Ainsworth AM, Akulov A, Alvarado P, Armada F, Assyov B, Avchar R, Avesani M, Bezerra JL, Bhat JD, Bilański P, Bily DS, Boccardo F, Bozok F, Campos JC, Chaimongkol S, Chellappan N, Costa MM, Dalecká M, Darmostuk V, Daskalopoulos V, Dearnaley J, Dentinger BTM, De Silva NI, Dhotre D, Carlavilla JR, Doungsa-ard C, Dovana F, Erhard A, Ferro LO, Gallegos SC, Giles CE, Gore G, Gorfer M, Guard FE, Hanson S-A, Haridev P, Jankowiak R, Jeffers SN, Kandemir H, Karich A, Kisło K, Kiss L, Krisai-Greilhuber I, Latha KPD, Lorenzini M, Lumyong S, Manimohan P, Manjón JL, Maula F, Mazur E, Mesquita NLS, Młynek K, Mongkolsamrit S, Morán P, Murugadoss R, Nagarajan M, Nalumpang S, Noisripoom W, Nosalj S, Novaes QS, Nowak M, Pawłowska J, Peiger M, Pereira OL, Pinto A, Plaza M, Polemis E, Polhorský A, Ramos DO, Raza M, Rivas-Ferreiro M, Rodriguez-Flakus P, Ruszkiewicz-Michalska M, Sánchez A, Santos A, Schüller A, Scott PA, Şen İ, Shelke D, Śliwa L, Solheim H, Sonawane H, Strašiftáková D, Stryjak-Bogacka M, Sudsanguan M, Suwannarach N, Suz LM, Syme K, Taşkın H, Tennakoon DS, Tomka P, Vaghefi N, Vasan V, Vauras J, Wiktorowicz D, Villarreal M, Vizzini A, Wrzosek M, Yang X, Yingkunchao W, Zapparoli G, Zervakis GI, Groenewald JZ (2024). Fungal Planet description sheets: 1614-1696. Fungal Systematics and Evolution 13: 183-440. doi: 10.3114/fuse.2024.13.11.

PMID:39140100 | PMC:PMC11320056 | DOI:10.3114/fuse.2024.13.11

Front Public Health. 2024 Jul 30;12:1406315. doi: 10.3389/fpubh.2024.1406315. eCollection 2024.

ABSTRACT

INTRODUCTION: Vaccination has been implemented as a useful measure to combat the COVID-19 pandemic. However, there is a tendency for individuals to avoid vaccination due to the possibility of adverse events, making it important to investigate the relationship between COVID-19 vaccines and their adverse events. This study explored longitudinal adverse event patterns and factors that influence adverse events following the second to fourth doses of the COVID-19 vaccine through a latent class analysis.

METHODS: Participants were recruited from the Fukushima Prefecture and included individuals who had completed four doses of the COVID-19 mRNA vaccine. This study utilized data from questionnaire surveys and blood collection conducted between September 2021 and November 2022. In the questionnaire, factors such as sex, age, medical history, medication, type of vaccine administered, and adverse events following vaccination were recorded. Additionally, in the blood data, serological tests [IgG(S)] and cellular immune responses (T-spot) were measured. Descriptive statistics, latent class analysis, multivariable logistic regression, and multiple regression analyses were performed to identify the longitudinal adverse event patterns and influencing factors. By analyzing adverse events over time, we identified two distinct groups: those less prone to experiencing adverse events (Group 1) and those more susceptible (Group 2) to latent class analysis.

RESULTS: A total of 1,175 participants were included after excluding those without any adverse events. The median age of the participants in Group 1 was 70 years, and in Group 2 it was 51 years. The proportion of female participants was 298 in Group 1 and 353 in Group 2. Patients in Group 2 were significantly younger (p < 0.001) and more likely to be female (p < 0.001) than those in Group 1. Furthermore, the median IgG(S) value after the fourth vaccination was 3,233 AU/mL in Group 1 and 4,059.39 AU/mL in Group 2. The median T-spot value was 15.4 in Group 1 and 28.5 in Group 2. Group 2 showed significantly higher IgG(S) and T-spot values after the fourth vaccination (p < 0.001).

DISCUSSION: Our findings suggest that factors other than age, particularly sex and a history of allergies, significantly influence the likelihood of experiencing adverse events. Groups categorized by latent class analysis for longitudinal adverse events are expected to be valuable for optimizing vaccination strategies and formulating public health measures.

PMID:39139673 | PMC:PMC11320210 | DOI:10.3389/fpubh.2024.1406315

iScience. 2024 Jul 15;27(8):110520. doi: 10.1016/j.isci.2024.110520. eCollection 2024 Aug 16.

ABSTRACT

A tissue resident-like phenotype in tumor infiltrating T cells can limit systemic anti-tumor immunity. Enhanced systemic anti-tumor immunity is observed in head and neck cancer patients after neoadjuvant PD-L1 immune checkpoint blockade (ICB) and transforming growth factor β (TGF-β) neutralization. Using T cell receptor (TCR) sequencing and functional immunity assays in a syngeneic model of oral cancer, we dissect the relative contribution of these treatments to enhanced systemic immunity. The addition of TGF-β neutralization to ICB resulted in the egress of expanded and exhausted CD8+ tumor infiltrating lymphocytes (TILs) into circulation and greater systemic anti-tumor immunity. This enhanced egress associated with reduced expression of Itgae (CD103) and its upstream regulator Znf683. Circulating CD8+ T cells expressed higher Cxcr3 after treatment, an observation also made in samples from patients treated with dual TGF-β neutralization and ICB. These findings provide the scientific rationale for the use of PD-L1 ICB and TGF-β neutralization in newly diagnosed patients with carcinomas prior to definitive treatment of locoregional disease.

PMID:39139402 | PMC:PMC11321305 | DOI:10.1016/j.isci.2024.110520

Genetics. 2024 Aug 14:iyae135. doi: 10.1093/genetics/iyae135. Online ahead of print.

ABSTRACT

Patterns of lineal descent play a critical role in the development of metazoan embryos. In eutelic organisms that generate a fixed number of somatic cells, invariance in the topology of their cell lineage provides a powerful opportunity to interrogate developmental events with empirical repeatability across individuals. Studies of embryonic development using the nematode Caenorhabditis elegans have been drivers of discovery. These studies have depended heavily on high throughput lineage tracing enabled by 4D fluorescence microscopy and robust computer vision pipelines. For a range of applications, computer-aided yet manual lineage tracing using 4D label-free microscopy remains an essential tool. Deep learning approaches to cell detection and tracking in fluorescence microscopy have advanced significantly in recent years, yet solutions for automating cell detection and tracking in 3D label-free imaging of dense tissues and embryos remain inaccessible. Here we describe embGAN, a deep learning pipeline that addresses the challenge of automated cell detection and tracking in label-free 3D time lapse imaging. embGAN requires no manual data annotation for training, learns robust detections that exhibits a high degree of scale invariance and generalizes well to images acquired in multiple labs on multiple instruments. We characterize embGAN's performance using lineage tracing in the C. elegans embryo as a benchmark. embGAN achieves near state-of-the-art performance in cell detection and tracking, enabling high-throughput studies of cell lineage without the need for fluorescent reporters or transgenics.

PMID:39139100 | DOI:10.1093/genetics/iyae135

Genetics. 2024 Aug 14:iyae134. doi: 10.1093/genetics/iyae134. Online ahead of print.

ABSTRACT

We present a geometry-based interpretation of the f-statistics framework, commonly used in population genetics to estimate phylogenetic relationships from genomic data. The focus is on the determination of the mixing coefficients in population admixture events subject to post-admixture drift. The interpretation takes advantage of the high dimension of the dataset and analyzes the problem as a dimensional reduction issue. We show that it is possible to think of the f-statistics technique as an implicit transformation of the genomic data from a phase space into a subspace where the mapped data structure is more similar to the ancestral admixture configuration. The two-way mixing coefficient is, as a matter of fact, carried out implicitly in this subspace. In addition, we propose the admixture test to be evaluated in the subspace because the comparison with the conventional one provides an important assessment of the admixture model. The overarching geometric framework provides slightly more general formulas than the f-formalism by using a different rationale as a starting point. Explicitly addressed are two-way and three-way admixtures. The mixture proportions are provided by suitable linear fits, in two or three dimensions, that can be easily visualized. The difficulties encountered with introgression and gene flow are also addressed. The developments and findings are illustrated with numerical simulations and real-world cases.

PMID:39138842 | DOI:10.1093/genetics/iyae134

Nat Commun. 2024 Aug 13;15(1):6946. doi: 10.1038/s41467-024-51213-z.

ABSTRACT

Hypervirulent Klebsiella pneumoniae (HvKP) is an emerging bacterial pathogen causing invasive infection in immune-competent humans. The hypervirulence is strongly linked to the overproduction of hypermucoviscous capsule, but the underlying regulatory mechanisms of hypermucoviscosity (HMV) have been elusive, especially at the post-transcriptional level mediated by small noncoding RNAs (sRNAs). Using a recently developed RNA interactome profiling approach iRIL-seq, we interrogate the Hfq-associated sRNA regulatory network and establish an intracellular RNA-RNA interactome in HvKP. Our data reveal numerous interactions between sRNAs and HMV-related mRNAs, and identify a plethora of sRNAs that repress or promote HMV. One of the strongest HMV repressors is ArcZ, which is activated by the catabolite regulator CRP and targets many HMV-related genes including mlaA and fbp. We discover that MlaA and its function in phospholipid transport is crucial for capsule retention and HMV, inactivation of which abolishes Klebsiella virulence in mice. ArcZ overexpression drastically reduces bacterial burden in mice and reduces HMV in multiple hypervirulent and carbapenem-resistant clinical isolates, indicating ArcZ is a potent RNA inhibitor of bacterial pneumonia with therapeutic potential. Our work unravels a novel CRP-ArcZ-MlaA regulatory circuit of HMV and provides mechanistic insights into the posttranscriptional virulence control in a superbug of global concern.

PMID:39138169 | DOI:10.1038/s41467-024-51213-z