Bioinformatics. 2024 Apr 3:btae182. doi: 10.1093/bioinformatics/btae182. Online ahead of print.

ABSTRACT

MOTIVATION: Long read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g. sequencing mutagenized libraries where multiple distinct clones differ by one or few variants, require the use of barcodes or unique molecular identifiers. Unfortunately, sequencing errors can interfere with correct barcode identification, and a given barcode sequence may be linked to multiple independent clones within a given library.

RESULTS: Here we focus on the target application of sequencing mutagenized libraries in the context of multiplexed assays of variant effects (MAVEs). MAVEs are increasingly used to create comprehensive genotype-phenotype maps that can aid clinical variant interpretation. Many MAVE methods use long-read sequencing of barcoded mutant libraries for accurate association of barcode with genotype. Existing long-read sequencing pipelines do not account for inaccurate sequencing or non-unique barcodes. Here, we describe Pacybara, which handles these issues by clustering long reads based on the similarities of (error-prone) barcodes while also detecting barcodes that have been associated with multiple genotypes. Pacybara also detects recombinant (chimeric) clones and reduces false positive indel calls. In three example applications, we show that Pacybara identifies and correctly resolves these issues.

AVAILABILITY: Pacybara, freely available at https://github.com/rothlab/pacybara, is implemented using R, Python and bash for Linux. It runs on GNU/Linux HPC clusters via Slurm, PBS, or GridEngine schedulers. A single-machine simplex version is also available.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38569896 | DOI:10.1093/bioinformatics/btae182

Cell Host Microbe. 2024 Mar 12:S1931-3128(24)00058-1. doi: 10.1016/j.chom.2024.02.015. Online ahead of print.

ABSTRACT

Microbiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk. To compare microbiota development across feeding modes, this randomized controlled intervention study (German Clinical Trial DRKS00012313) longitudinally sampled infant stool during the first year of life, revealing similar fecal bacterial communities between formula- and breast-fed infants (N = 210) but differences across age. Infant formula containing GOS sustained high levels of bifidobacteria compared with formula containing B. longum and B. breve or placebo. Metabolite and bacterial profiling revealed 24-h oscillations and circadian networks. Rhythmicity in bacterial diversity, specific taxa, and functional pathways increased with age and was strongest following breastfeeding and GOS supplementation. Circadian rhythms in dominant taxa were further maintained ex vivo in a chemostat model. Hence, microbiota rhythmicity develops early in life and is impacted by diet.

PMID:38569545 | DOI:10.1016/j.chom.2024.02.015

Cell Metab. 2024 Apr 2;36(4):857-876.e10. doi: 10.1016/j.cmet.2024.02.007.

ABSTRACT

Leptin resistance during excess weight gain significantly contributes to the recidivism of obesity to leptin-based pharmacological therapies. The mechanisms underlying the inhibition of leptin receptor (LepR) signaling during obesity are still elusive. Here, we report that histone deacetylase 6 (HDAC6) interacts with LepR, reducing the latter's activity, and that pharmacological inhibition of HDAC6 activity disrupts this interaction and augments leptin signaling. Treatment of diet-induced obese mice with blood-brain barrier (BBB)-permeable HDAC6 inhibitors profoundly reduces food intake and leads to potent weight loss without affecting the muscle mass. Genetic depletion of Hdac6 in Agouti-related protein (AgRP)-expressing neurons or administration with BBB-impermeable HDAC6 inhibitors results in a lack of such anti-obesity effect. Together, these findings represent the first report describing a mechanistically validated and pharmaceutically tractable therapeutic approach to directly increase LepR activity as well as identifying centrally but not peripherally acting HDAC6 inhibitors as potent leptin sensitizers and anti-obesity agents.

PMID:38569472 | DOI:10.1016/j.cmet.2024.02.007

Food Chem. 2024 Mar 28;448:139157. doi: 10.1016/j.foodchem.2024.139157. Online ahead of print.

ABSTRACT

About half of the world's population is infected with the bacterium Helicobacter pylori. For colonization, the bacterium neutralizes the low gastric pH and recruits immune cells to the stomach. The immune cells secrete cytokines, i.e., the pro-inflammatory IL-17A, which directly or indirectly damage surface epithelial cells. Since (I) dietary proteins are known to be digested into bitter tasting peptides in the gastric lumen, and (II) bitter tasting compounds have been demonstrated to reduce the release of pro-inflammatory cytokines through functional involvement of bitter taste receptors (TAS2Rs), we hypothesized that the sweet-tasting plant protein thaumatin would be cleaved into anti-inflammatory bitter peptides during gastric digestion. Using immortalized human parietal cells (HGT-1 cells), we demonstrated a bitter taste receptor TAS2R16-dependent reduction of a H. pylori-evoked IL-17A release by up to 89.7 ± 21.9% (p ≤ 0.01). Functional involvement of TAS2R16 was demonstrated by the study of specific antagonists and siRNA knock-down experiments.

PMID:38569411 | DOI:10.1016/j.foodchem.2024.139157

Genome Biol. 2024 Apr 3;25(1):85. doi: 10.1186/s13059-024-03227-5.

ABSTRACT

Cell type annotation and lineage construction are two of the most critical tasks conducted in the analyses of single-cell RNA sequencing (scRNA-seq). Four recent scRNA-seq studies of differentiating xylem propose four models on differentiating xylem development in Populus. The differences are mostly caused by the use of different strategies for cell type annotation and subsequent lineage interpretation. Here, we emphasize the necessity of using in situ transcriptomes and anatomical information to construct the most plausible xylem development model.

PMID:38570851 | DOI:10.1186/s13059-024-03227-5

Nat Microbiol. 2024 Apr 3. doi: 10.1038/s41564-024-01639-4. Online ahead of print.

ABSTRACT

Globally, half a billion people are employed in animal agriculture and are directly exposed to the associated microorganisms. However, the extent to which such exposures affect resident human microbiomes is unclear. Here we conducted a longitudinal profiling of the nasal and faecal microbiomes of 66 dairy farmers and 166 dairy cows over a year-long period. We compare farmer microbiomes to those of 60 age-, sex- and ZIP code-matched people with no occupational exposures to farm animals (non-farmers). We show that farming is associated with microbiomes containing livestock-associated microbes; this is most apparent in the nasal bacterial community, with farmers harbouring a richer and more diverse nasal community than non-farmers. Similarly, in the gut microbial communities, we identify more shared microbial lineages between cows and farmers from the same farms. Additionally, we find that shared microbes are associated with antibiotic resistance genes. Overall, our study demonstrates the interconnectedness of human and animal microbiomes.

PMID:38570675 | DOI:10.1038/s41564-024-01639-4

Nat Cell Biol. 2024 Apr 3. doi: 10.1038/s41556-024-01380-4. Online ahead of print.

ABSTRACT

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.

PMID:38570617 | DOI:10.1038/s41556-024-01380-4

Nat Commun. 2024 Apr 3;15(1):2889. doi: 10.1038/s41467-024-47288-3.

NO ABSTRACT

PMID:38570501 | DOI:10.1038/s41467-024-47288-3

Cell Mol Life Sci. 2024 Apr 4;81(1):163. doi: 10.1007/s00018-024-05201-7.

ABSTRACT

Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known. In this study, we applied high-resolution proteomics to murine and human iRhom2-deficient macrophages for a systematic identification of substrates, and therefore functions, of the iRhom2/ADAM17 proteolytic complex. We found that iRhom2 loss suppressed the release of a group of transmembrane proteins, including known (e.g. CSF1R) and putative novel ADAM17 substrates. In the latter group, shedding of major histocompatibility complex class I molecules (MHC-I) was consistently reduced in both murine and human macrophages when iRhom2 was ablated. Intriguingly, it emerged that in addition to its shedding, iRhom2 could also control surface expression of MHC-I by an undefined mechanism. We have demonstrated the biological significance of this process by using an in vitro model of CD8+ T-cell (CTL) activation. In this model, iRhom2 loss and consequent reduction of MHC-I expression on the cell surface of an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line dampened activation of autologous CTLs and their cell-mediated cytotoxicity. Taken together, this study uncovers a new role for iRhom2 in controlling cell surface levels of MHC-I by a dual mechanism that involves regulation of their surface expression and ectodomain shedding.

PMID:38570362 | DOI:10.1007/s00018-024-05201-7

Pflugers Arch. 2024 Apr 4. doi: 10.1007/s00424-024-02953-w. Online ahead of print.

ABSTRACT

Mammalian cells utilize glucose as a primary carbon source to produce energy for most cellular functions. However, the bioenergetic homeostasis of cells can be perturbed by environmental alterations, such as changes in oxygen levels which can be associated with bacterial infection. Reduction in oxygen availability leads to a state of hypoxia, inducing numerous cellular responses that aim to combat this stress. Importantly, hypoxia strongly augments cellular glycolysis in most cell types to compensate for the loss of aerobic respiration. Understanding how this host cell metabolic adaptation to hypoxia impacts the course of bacterial infection will identify new anti-microbial targets. This review will highlight developments in our understanding of glycolytic substrate channeling and spatiotemporal enzymatic organization in response to hypoxia, shedding light on the integral role of the hypoxia-inducible factor (HIF) during host-pathogen interactions. Furthermore, the ability of intracellular and extracellular bacteria (pathogens and commensals alike) to modulate host cellular glucose metabolism will be discussed.

PMID:38570355 | DOI:10.1007/s00424-024-02953-w

PLoS One. 2024 Apr 3;19(4):e0301330. doi: 10.1371/journal.pone.0301330. eCollection 2024.

ABSTRACT

The ongoing COVID-19 pandemic has led to the emergence of new SARS-CoV-2 variants as a result of continued host-virus interaction and viral genome mutations. These variants have been associated with varying levels of transmissibility and disease severity. We investigated the phenotypic profiles of six SARS-CoV-2 variants (WT, D614G, Alpha, Beta, Delta, and Omicron) in Calu-3 cells, a human lung epithelial cell line. In our model demonstrated that all variants, except for Omicron, had higher efficiency in virus entry compared to the wild-type. The Delta variant had the greatest phenotypic advantage in terms of early infection kinetics and marked syncytia formation, which could facilitate cell-to-cell spreading, while the Omicron variant displayed slower replication and fewer syncytia formation. We also identified the Delta variant as the strongest inducer of inflammatory biomarkers, including pro-inflammatory cytokines/chemokines (IP-10/CXCL10, TNF-α, and IL-6), anti-inflammatory cytokine (IL-1RA), and growth factors (FGF-2 and VEGF-A), while these inflammatory mediators were not significantly elevated with Omicron infection. These findings are consistent with the observations that there was a generally more pronounced inflammatory response and angiogenesis activity within the lungs of COVID-19 patients as well as more severe symptoms and higher mortality rate during the Delta wave, as compared to less severe symptoms and lower mortality observed during the current Omicron wave in Thailand. Our findings suggest that early infectivity kinetics, enhanced syncytia formation, and specific inflammatory mediator production may serve as predictive indicators for the virulence potential of future SARS-CoV-2 variants.

PMID:38568894 | DOI:10.1371/journal.pone.0301330

Am J Respir Crit Care Med. 2024 Apr 3. doi: 10.1164/rccm.202307-1310OC. Online ahead of print.

ABSTRACT

RATIONALE: Idiopathic Pulmonary Arterial Hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling due to plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia.

OBJECTIVE: Test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries.

METHODS: We used digital spatial transcriptomics to profile the genome-wide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n= 11) and compared these data to the intima+media and adventitia of control pulmonary artery (n=5).

RESULTS: We detected 8273 transcripts in the IPAH lesions and control lung pulmonary arteries. Plexiform lesions and IPAH adventitia exhibited the greatest number of differentially expressed genes when compared with intima-media hypertrophy and obliterative lesions. Plexiform lesions in IPAH showed enrichment for (i) genes associated with TGFβ-signaling and (ii) mutated genes affecting the extracellular matrix and endothelial-mesenchymal transformation. Plexiform lesions and IPAH adventitia showed upregulation of genes involved in immune and interferon signaling, coagulation, and complement pathways. Cellular deconvolution indicated variability in the number of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcript profiling.

CONCLUSIONS: IPAH lesions express unique molecular transcript profiles enriched for pathways involving pathogenetic pathways, including genetic disease drivers, innate and acquired immunity, hypoxia sensing, and angiogenesis signaling. These data provide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and therapeutic targets in this highly morbid disease.

PMID:38568479 | DOI:10.1164/rccm.202307-1310OC

J Virol. 2024 Apr 3:e0151623. doi: 10.1128/jvi.01516-23. Online ahead of print.

ABSTRACT

The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed the evaluation of the safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a systems biology approach to compare hematological, biochemical, transcriptomic, and innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans but with a slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques [by Day 7[(D7)], but titers > 10 were reached in both species by D14 post-vaccination and were not significantly different by D28 [plaque reduction neutralization assay (PRNT)50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; P = 0.821]. Changes in neutrophils, NK cells, monocytes, and T- and B-cell frequencies were higher in cynomolgus macaques and persisted for 4 weeks versus less than 2 weeks in humans. Low levels of systemic inflammatory cytokines (IL-1RA, IL-8, MIP-1α, IP-10, MCP-1, or VEGF) were detected in either or both species but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3-D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low-level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques [28% (5/18)] but generally absent in humans [except one participant (5%; 1/20)].IMPORTANCECynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans and suggest a key role for type I IFN.

PMID:38567951 | DOI:10.1128/jvi.01516-23

Nucleic Acids Res. 2024 Apr 3:gkae243. doi: 10.1093/nar/gkae243. Online ahead of print.

ABSTRACT

Bacterial defence systems are tightly regulated to avoid autoimmunity. In Type I restriction-modification (R-M) systems, a specific mechanism called restriction alleviation (RA) controls the activity of the restriction module. In the case of the Escherichia coli Type I R-M system EcoKI, RA proceeds through ClpXP-mediated proteolysis of restriction complexes bound to non-methylated sites that appear after replication or reparation of host DNA. Here, we show that RA is also induced in the presence of plasmids carrying EcoKI recognition sites, a phenomenon we refer to as plasmid-induced RA. Further, we show that the anti-restriction behavior of plasmid-borne non-conjugative transposons such as Tn5053, previously attributed to their ardD loci, is due to plasmid-induced RA. Plasmids carrying both EcoKI and Chi sites induce RA in RecA- and RecBCD-dependent manner. However, inactivation of both RecA and RecBCD restores RA, indicating that there exists an alternative, RecA-independent, homologous recombination pathway that is blocked in the presence of RecBCD. Indeed, plasmid-induced RA in a RecBCD-deficient background does not depend on the presence of Chi sites. We propose that processing of random dsDNA breaks in plasmid DNA via homologous recombination generates non-methylated EcoKI sites, which attract EcoKI restriction complexes channeling them for ClpXP-mediated proteolysis.

PMID:38567730 | DOI:10.1093/nar/gkae243

Plant Cell. 2024 Apr 3:koae102. doi: 10.1093/plcell/koae102. Online ahead of print.

ABSTRACT

Cyanobacteria and chloroplasts of algae and plants harbor specialized thylakoid membranes that convert sunlight into chemical energy. These membranes house photosystems II and I, the vital protein-pigment complexes that drive oxygenic photosynthesis. In the course of their evolution, thylakoid membranes have diversified in structure. However, the core machinery for photosynthetic electron transport remained largely unchanged, with adaptations occurring primarily in the light-harvesting antenna systems. Whereas thylakoid membranes in cyanobacteria are relatively simple they become more complex in algae and plants. The chloroplasts of vascular plants contain intricate networks of stacked grana and unstacked stroma thylakoids. This review provides an in-depth view of thylakoid membrane architectures in phototrophs, and the determinants that shape their forms, as well as presenting recent insights into the spatial organization of their biogenesis and maintenance. Its overall goal is to define the underlying principles that have guided the evolution of these bioenergetic membranes.

PMID:38567528 | DOI:10.1093/plcell/koae102

Phys Chem Chem Phys. 2024 Apr 3. doi: 10.1039/d3cp06051a. Online ahead of print.

ABSTRACT

The intramolecular Stetter reaction catalyzed by a carbene is investigated by density functional theory (DFT) calculations and kinetic simulations. Catalyst 1 first reacts with aldehyde 2 to give the primary adduct (PA). The PA undergoes the intramolecular oxa-Michael reaction to irreversibly generate enol ether intermediate 9. The conversion of the enol ether to the Breslow intermediate (BI) requires the assistance of a base such as the PA. The next step involves formation of a carbon-carbon bond through the Michael addition, and expulsion of the catalyst generates the Stetter product 7. Calculations show that the catalytic cycle is composed of two irreversible processes: the first one involves the exergonic formation of the enol ether intermediate, while the second one is the conversion of the enol ether to the final product. Kinetic simulations using initial concentrations of [1]0 = 0.005 M and [2]0 = 0.025 M demonstrate that under a steady-state condition, 35% of the catalyst rests on the state of the enol ether (0.0018 M). The catalyst resting state therefore consists of the unbound form (the free catalyst) and its bound form (the enol ether species). According to variable time normalization analysis, the reaction exhibits a second-order dependence (first order in catalyst and first order in substrate), which agrees with experiments. The oxa-Michael reaction to form the enol ether is identified to be turnover limiting in the intramolecular Stetter reaction, which rationalizes the observed electronic effect of the Michael acceptor on the reactivity, as well as the measured isotope effect with respect to the aldehydic proton/deuteron. The base that participates in the BI formation has a significant effect on the build-up of the resting state 9 and the active catalyst concentration. In addition, the thermodynamic stability of the enol ether is found to depend on the tether length between the aromatic aldehyde and the Michael acceptor, as well as the chemical nature of the carbene catalyst. The favorability for the oxa-Michael reaction is therefore suggested to govern the reactivity of the intramolecular Stetter transformation.

PMID:38567403 | DOI:10.1039/d3cp06051a

Persoonia. 2023 Jun;50:48-122. doi: 10.3767/persoonia.2023.50.03. Epub 2023 May 12.

ABSTRACT

Type material and additional collections of 11 taxa of Gautieria described in Europe and North Africa have been studied, namely G. dubia, G. graveolens, G. morchelliformis var. globispora, G. morchelliformis var. magnicellaris, G. morchelliformis var. morchelliformis, G. morchelliformis var. stenospora, G. otthii, G. pseudovestita, G. retirugosa, G. trabutii and G. villosa. At the same time, morphological and genetic studies on recent and herbarium collections from several European countries have been carried out. This enabled clarification of sections within Gautieria and differentiation of 28 taxa, of which 21 are new to science. However, the deeper relationships and nomenclature changes related to the phylogenetic position of the genus Gautieria within Gomphaceae will not be addressed in this study because they would require a more complete molecular analysis together with that of related genera, e.g., Gomphus, Turbinellus, and the four subgenera of Ramaria. In addition, a lectotype for G. villosa var. villosa and reference specimens for G. graveolens and G. morchelliformis var. morchelliformis are selected, and the new combination G. morchelliformis var. dubia is proposed. Detailed descriptions, macro- and microphotographs and distribution maps of all taxa are provided, as well as extensive information on their ecology, chorology and phylogeny. A key is included to facilitate identification of taxa. Citation: Vidal JM, Cseh P, Merényi Z, et al. 2023. The genus Gautieria (Gomphales) in Europe and the Mediterranean Basin: a morphological and phylogenetic taxonomic revision. Persoonia 50: 48 -122. https://doi.org/10.3767/persoonia.2023.50.03.

PMID:38567262 | PMC:PMC10983841 | DOI:10.3767/persoonia.2023.50.03

Persoonia. 2023 Jun;50:123-157. doi: 10.3767/persoonia.2023.50.04. Epub 2023 Jun 20.

ABSTRACT

A revision, based on morphological and multigene analysis, of the Clitocella species currently present in Europe is provided. Portions of nrITS rDNA, nr28S rDNA (LSU), RNA polymerase II second largest subunit (RPB2), translation elongation factor 1-alpha (EF-1α), and ATPase subunit 6 (ATP6), were used to sort out the relationships of the species within the genus. Three subgenera were recognized: Clitocella subg. Clitocella encompassing C. popinalis, C. colorata, C. mundula, C. nigrescens, C. obscura and the new species C. solaris from Switzerland; the new Clitocella subg. Paraclitopilus including C. fallax and C. blancii; and the new Clitocella subg. Rhodopleurella for accommodating C. termitophila, a peculiar entity characterized by a pleurotoid habit and growing on decaying, abandoned termite nests in the Dominican Republic. Clitocella colorata originally described from China is here reported and described for the first time in Europe (Italy and Estonia). Rhodocybe cupressicola and Clitopilus ammophilus are reduced to later synonyms of Rhodopaxillus nigrescens; similarly, Clitopilus amarus is treated as a later synonym of Omphalia fallax while Rhodocybe amarella and R. ochraceopallida of Rhodopaxillus blancii. Finally, Austrian and Swedish herbarium collections identified as Rhodocybe, a doubtful taxon considered by several modern authors occasionally as either a similar but distinct species from R. popinalis or as a dwarfish, puny and odourless form of R. popinalis, have been proved to be R. tugrulii, a species recently described from Turkey and Estonia, and also later reported from Italy and USA. Citation: Vizzini A, Consiglio G, Marchetti M. 2023. Overview of the European species of the genus Clitocella (Entolomataceae, Agaricales) with notes on extralimital taxa. Persoonia 50: 123-157. https://doi.org/10.3767/persoonia.2023.50.04.

PMID:38567261 | PMC:PMC10983838 | DOI:10.3767/persoonia.2023.50.04

Plant J. 2024 Apr 2. doi: 10.1111/tpj.16754. Online ahead of print.

ABSTRACT

The Arabidopsis endoplasmic reticulum-localized heat shock protein HSP90.7 modulates tissue differentiation and stress responses; however, complete knockout lines have not been previously reported. In this study, we identified and analyzed a mutant allele, hsp90.7-1, which was unable to accumulate the HSP90.7 full-length protein and showed seedling lethality. Microscopic analyses revealed its essential role in male and female fertility, trichomes and root hair development, proper chloroplast function, and apical meristem maintenance and differentiation. Comparative transcriptome and proteome analyses also revealed the role of the protein in a multitude of cellular processes. Particularly, the auxin-responsive pathway was specifically downregulated in the hsp90.7-1 mutant seedlings. We measured a much-reduced auxin content in both root and shoot tissues. Through comprehensive histological and molecular analyses, we confirmed PIN1 and PIN5 accumulations were dependent on the HSP90 function, and the TAA-YUCCA primary auxin biosynthesis pathway was also downregulated in the mutant seedlings. This study therefore not only fulfilled a gap in understanding the essential role of HSP90 paralogs in eukaryotes but also provided a mechanistic insight on the ER-localized chaperone in regulating plant growth and development via modulating cellular auxin homeostasis.

PMID:38565312 | DOI:10.1111/tpj.16754

Cell Genom. 2024 Mar 26:100538. doi: 10.1016/j.xgen.2024.100538. Online ahead of print.

ABSTRACT

Nearly all trait-associated variants identified in genome-wide association studies (GWASs) are noncoding. The cis regulatory effects of these variants have been extensively characterized, but how they affect gene regulation in trans has been the subject of fewer studies because of the difficulty in detecting trans-expression quantitative loci (eQTLs). We developed trans-PCO for detecting trans effects of genetic variants on gene networks. Our simulations demonstrate that trans-PCO substantially outperforms existing trans-eQTL mapping methods. We applied trans-PCO to two gene expression datasets from whole blood, DGN (N = 913) and eQTLGen (N = 31,684), and identified 14,985 high-quality trans-eSNP-module pairs associated with 197 co-expression gene modules and biological processes. We performed colocalization analyses between GWAS loci of 46 complex traits and the trans-eQTLs. We demonstrated that the identified trans effects can help us understand how trait-associated variants affect gene regulatory networks and biological pathways.

PMID:38565144 | DOI:10.1016/j.xgen.2024.100538