Acarospora socialis, the bright cobblestone lichen, is commonly found in southwestern North America. This charismatic yellow lichen is a species of key ecological significance as it is often a pioneer species in new environments. Despite their ecological importance virtually no research has been conducted on the genomics of A. socialis. To address this, we used long-read sequencing to generate the first high-quality draft genome of A. socialis. Lichen thallus tissue was collected from Pinkham Canyon in Joshua Tree National Park, California and deposited in the UC Riverside herbarium under accession #295874. The de novo assembly of the mycobiont partner of the lichen was generated from Pacific Biosciences HiFi long reads and Dovetail Omni-C chromatin capture data. After removing algal and bacterial contigs, the fungal genome was approximately 31.2 Mb consisting of 38 scaffolds with contig and scaffold N50 of 2.4 Mb. The BUSCO completeness score of the assembled genome was 97.5% using the Ascomycota gene set. Information on the genome of A. socialis is important for California conservation purposes given that this lichen is threatened in some places locally by wildfires due to climate change. This reference genome will be used for understanding the genetic diversity, population genomics, and comparative genomics of A. socialis species. Genomic resources for this species will support population and landscape genomics investigations, exploring the use of A. socialis as a bioindicator species for climate change, and in studies of adaptation by comparing populations that occur across aridity gradients in California.
Gene prediction is required to obtain optimal biologically meaningful information from genomic sequences, but automated gene prediction software is imperfect. In this study, we compare the original annotation of the Coccidioides immitis RS genome (the reference strain of C. immitis) to annotations using the Funannotate and Augustus genome prediction pipelines. A total of 25% of the originally predicted genes (denoted CIMG) were not found in either the Funannotate or Augustus predictions. A comparison of Funannotate and Augustus predictions also found overlapping but not identical sets of genes. The predicted genes found only in the original annotation (referred to as CIMG-unique) were less likely to have a meaningful functional annotation and a lower number of orthologs and homologs in other fungi than all CIMG genes predicted by the original annotation. The CIMG-unique genes were also more likely to be lineage-specific and poorly expressed. In addition, the CIMG-unique genes were found in clusters and tended to be more frequently associated with transposable elements than all CIMG-predicted genes. The CIMG-unique genes were more likely to have experimentally determined transcription start sites that were further away from the originally predicted transcription start sites, and experimentally determined initial transcription was less likely to result in stable CIMG-unique transcripts. A sample of CIMG-unique genes that were relatively well expressed and differentially expressed in mycelia and spherules was inspected in a genome browser, and the structure of only about half of them was found to be supported by RNA-seq data. These data suggest that some of the CIMG-unique genes are not authentic gene predictions. Genes that were predicted only by the Funannotate pipeline were also less likely to have a meaningful functional annotation, be shorter, and express less well than all the genes predicted by Funannotate. C. immitis genes predicted by more than one annotation are more likely to have predicted functions, many orthologs and homologs, and be well expressed. Lineage-specific genes are relatively uncommon in this group. These data emphasize the importance and limitations of gene prediction software and suggest that improvements to the annotation of the C. immitis genome should be considered.
Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.
We present model constraints on the atmospheric structure of HD 106906 b, a planetary-mass companion orbiting at a ∼700 au projected separation around a 15 Myr old stellar binary, using the APOLLO retrieval code on spectral data spanning 1.1–2.5 μm. C/O ratios can provide evidence for companion formation pathways, as such pathways are ambiguous both at wide separations and at star-to-companion mass ratios in the overlap between the distributions of planets and brown dwarfs. We benchmark our code against an existing retrieval of the field L dwarf 2MASSW J2224–0158, returning a C/O ratio consistent with previous fits to the same JHK
data, but disagreeing in the thermal structure, cloud properties, and atmospheric scale height. For HD 106906 b, we retrieve C/O
, consistent with the C/O ratios expected for HD 106906's stellar association and therefore consistent with a stellar-like formation for the companion. We find abundances of H2O and CO near chemical equilibrium values for a solar metallicity but a surface gravity lower than expected, as well as a thermal profile with sharp transitions in the temperature gradient. Despite high signal-to-noise ratio and spectral resolution, more accurate constraints necessitate data across a broader wavelength range. This work serves as preparation for subsequent retrievals in the era of JWST, as JWST's spectral range provides a promising opportunity to resolve difficulties in fitting low-gravity L dwarfs and also underscores the need for simultaneous comparative retrievals on L-dwarf companions with multiple retrieval codes.
Digestion of waste feedstocks by larvae of the black soldier fly Hermetia illucens (Diptera: Stratiomyidae) (BSF) results in proteins for animal feed and organic fertilizer with a reduced environmental footprint, but it can still have negative environmental effects through greenhouse gas (GHG) and ammonia (NH3) emissions. Both biomass conversion by BSF larvae and associated GHG and NH3 emissions can depend on substrate properties that may be optimized through microbial inoculation pre-treatments, such as bokashi fermentation. Here, we quantified the effects of bokashi fermentation of brewery's spent grains on BSF rearing metrics and associated GHG and NH3 emissions at benchtop scale. We found that bokashi fermentation increased larval biomass by 40% and shortened development time by over two days on average, compared with unfermented spent grains. In line with increased larval growth, CO2 emissions in BSF larvae treatments were 31.0 and 79.0% higher in the bokashi fermented spent grains and Gainesville substrates, respectively, compared to the unfermented spent grains. Adding BSF larvae to the spent grains increased cumulative N2O emissions up to 64.0 mg N2O kg substratedry-1 but there were essentially no N2O emissions when larvae were added to fermented spent grains. Bokashi fermentation also reduced NH3 fluxes from the volatilization of substrate nitrogen in the BSF larvae treatment by 83.7-85.8% during days 7 and 9, possibly by increasing N assimilation by larvae or by reducing the transformation of substrate NH4+ to NH3. Therefore, bokashi fermentation may be applied to improve performance of BSF larvae on a common industrial waste stream and reduce associated emissions.
Malaria-associated pathogenesis such as parasite invasion, egress, host cell remodelling and antigenic variation requires concerted action by many proteins, but the molecular regulation is poorly understood. Here we have characterized an essential Plasmodium-specific Apicomplexan AP2 transcription factor in Plasmodium falciparum (PfAP2-P; pathogenesis) during the blood-stage development with two peaks of expression. An inducible knockout of gene function showed that PfAP2-P is essential for trophozoite development, and critical for var gene regulation, merozoite development and parasite egress. Chromatin immunoprecipitation sequencing data collected at timepoints matching the two peaks of pfap2-p expression demonstrate PfAP2-P binding to promoters of genes controlling trophozoite development, host cell remodelling, antigenic variation and pathogenicity. Single-cell RNA sequencing and fluorescence-activated cell sorting revealed de-repression of most var genes in Δpfap2-p parasites. Δpfap2-p parasites also overexpress early gametocyte marker genes, indicating a regulatory role in sexual stage conversion. We conclude that PfAP2-P is an essential upstream transcriptional regulator at two distinct stages of the intra-erythrocytic development cycle.
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a complex etiology that lacks biomarkers predicting disease progression. The objective of this study was to use longitudinal cerebrospinal fluid (CSF) samples to identify biomarkers that distinguish fast progression (FP) from slow progression (SP) and assess their temporal response. METHODS: We utilized mass spectrometry (MS)-based proteomics to identify candidate biomarkers using longitudinal CSF from a discovery cohort of SP and FP ALS patients. Immunoassays were used to quantify and validate levels of the top biomarkers. A state-transition mathematical model was created using the longitudinal MS data that also predicted FP versus SP. RESULTS: We identified a total of 1148 proteins in the CSF of all ALS patients. Pathway analysis determined enrichment of pathways related to complement and coagulation cascades in FPs and synaptogenesis and glucose metabolism in SPs. Longitudinal analysis revealed a panel of 59 candidate markers that could segregate FP and SP ALS. Based on multivariate analysis, we identified three biomarkers (F12, RBP4, and SERPINA4) as top candidates that segregate ALS based on rate of disease progression. These proteins were validated in the discovery and a separate validation cohort. Our state-transition model determined that the overall variance of the proteome over time was predictive of the disease progression rate. INTERPRETATION: We identified pathways and protein biomarkers that distinguish rate of ALS disease progression. A mathematical model of the CSF proteome determined that the change in entropy of the proteome over time was predictive of FP versus SP.
Microsatellite repeat expansions within genes contribute to a number of neurological diseases1,2. The accumulation of toxic proteins and RNA molecules with repetitive sequences, and/or sequestration of RNA-binding proteins by RNA molecules containing expanded repeats are thought to be important contributors to disease aetiology3-9. Here we reveal that the adenosine in CAG repeat RNA can be methylated to N1-methyladenosine (m1A) by TRMT61A, and that m1A can be demethylated by ALKBH3. We also observed that the m1A/adenosine ratio in CAG repeat RNA increases with repeat length, which is attributed to diminished expression of ALKBH3 elicited by the repeat RNA. Additionally, TDP-43 binds directly and strongly with m1A in RNA, which stimulates the cytoplasmic mis-localization and formation of gel-like aggregates of TDP-43, resembling the observations made for the protein in neurological diseases. Moreover, m1A in CAG repeat RNA contributes to CAG repeat expansion-induced neurodegeneration in Caenorhabditis elegans and Drosophila. In sum, our study offers a new paradigm of the mechanism through which nucleotide repeat expansion contributes to neurological diseases and reveals a novel pathological function of m1A in RNA. These findings may provide an important mechanistic basis for therapeutic intervention in neurodegenerative diseases emanating from CAG repeat expansion.