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Background Plant-parasitic nematodes (PPNs) that cause most damage include root-knot nematodes (RKNs) which are a major impediment to crop production. Root-knot nematodes, like other parasites, secrete proteins which are required for parasite proliferation and survival within the host during the infection process. Results Here, we used various computational tools to predict and identify classically and non-classically secreted proteins encoded in the Meloidogyne javanica genome. Furthermore, functional annotation analysis was performed using various integrated bioinformatic tools to determine the biological significance of the predicted secretome. In total, 7,458 proteins were identified as secreted ones. A large percentage of this secretome is comprised of small proteins of ≤ 300 aa sequence length. Functional analyses showed that M. javanica secretome comprises cell wall degrading enzymes for facilitating nematode invasion, and migration by disintegrating the complex plant cell wall components. In addition, peptidases and peptidase inhibitors are an important category of M. javanica secretome involved in compatible host-nematode interactions. Conclusion This study identifies the putative secretome encoded in the M. javanica genome. Future experimental validation analyses can greatly benefit from this global analysis of M. javanica secretome. Equally, our analyses will advance knowledge of the interaction between plants and nematodes.

Autorepression of PER-encoding genes underlies the periodic fluctuations in expression that drive the circadian clock. New work shows that histone deacetylase and histone methyltransferase activities are sequentially recruited to promoters of PER-encoding genes by separate PER protein–containing complexes and repress transcription via histone H3K9 modifications at those targets. The mammalian circadian clock is built on a molecular feedback loop in which the Period (PER) proteins, acting in a large, poorly understood complex, repress Clock–Bmal1, the transcription factor driving their expression. We found that mouse PER complexes include the histone methyltransferase HP1γ–Suv39h. PER proteins recruited HP1γ–Suv39h to the Per1 and Per2 promoters, and HP1γ–Suv39h proved important for circadian di- and trimethylation of histone H3 Lys9 (H3K9) at the Per1 promoter, feedback repression and clock function. HP1γ–Suv39h was recruited to the Per1 and Per2 promoters ~4 h after recruitment of HDAC1, a PER-associated protein previously implicated in clock function and H3K9 deacetylation at the Per1 promoter. PER complexes containing HDAC1 or HP1γ–Suv39h appeared to be physically separable. Circadian clock negative feedback by the PER complex thus involves dynamic, ordered recruitment of repressive chromatin modifiers to DNA-bound Clock–Bmal1.

Circadian rhythms in mammals are generated by a feedback loop in which the three PERIOD (PER) proteins, acting in a large complex, inhibit the transcriptional activity of the CLOCK-BMAL1 dimer, which represses their own expression. Although fundamental, the mechanism of negative feedback in the mammalian clock, or any eukaryotic clock, is unknown. We analyzed protein constituents of PER complexes purified from mouse tissues and identified PSF (polypyrimidine tract—binding protein—associated splicing factor). Our analysis indicates that PSF within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and that the PER complex thereby rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription. These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback.

Determining the best therapy for HIV-associated cryptococcal meningitis in resource-poor settings is controversial. In this trial in Vietnam, initial therapy with amphotericin B with flucytosine had better outcomes than amphotericin B alone or with fluconazole. There are approximately 1 million cases of cryptococcal meningitis annually and 625,000 deaths. 1 Treatment guidelines recommend induction therapy with amphotericin B deoxycholate (0.7 to 1 mg per kilogram of body weight per day) and flucytosine (100 mg per kilogram per day). 2 However, this treatment has not been shown to reduce mortality, as compared with amphotericin B monotherapy. 2 , 3 Flucytosine is frequently unavailable where the disease burden is greatest, and concerns about cost and side effects have limited its use in resource-poor settings. 4 Fluconazole is readily available, is associated with low rates of adverse events, and has good penetration into cerebrospinal . . .

Background Rhizina undulata is an important tree pathogen, infecting a wide variety of conifer species, including those in the genus Pinus . The fungus relies on heat shock-mediated activation of its ascospores, which require high temperatures to initiate germination. Consequently, disease due to R. undulata often occurs after fire events in both natural and managed forests. The genetic mechanisms contributing to the pyrophilous nature of R. undulata have not been investigated. We sought to identify key genes that may be responsible for thermotolerance in the fungus. A comparative genomics approach was used, by sequencing the genome of R. undulata for the first time and comparing its predicted proteome to those from other Pezizomycetes, both with and without known associations with fire. Results Three protein families were shown to be expanded in R. undulata ; heat shock protein 20 (HSP20), glutathione-S transferases (GST), and aromatic compound dioxygenases (ACD). While HSP20 was uniquely over-represented in R. undulata , the expansions of the GST and ACD families were also identified in other fire-associated species. Conclusion HSP20s are known to protect cells against heat stress, GSTs are involved in the detoxification of reactive oxygen species, and ACDs play a role in the metabolism of recalcitrant compounds present in post-fire environments. The expansion of these families thus suggests that they may play an important role in protecting and stimulating R. undulata ascospores during and after fire-induced heat shock, activating the fungus, and enabling it to colonise the root systems of conifers.

Background Phytophthora cinnamomi is an oomycete pathogen of global relevance. It is considered as one of the most invasive species, which has caused irreversible damage to natural ecosystems and horticultural crops. There is currently a lack of a high-quality reference genome for this species despite several attempts that have been made towards sequencing its genome. The lack of a good quality genome sequence has been a setback for various genetic and genomic research to be done on this species. As a consequence, little is known regarding its genome characteristics and how these contribute to its pathogenicity and invasiveness. Results In this work we generated a high-quality genome sequence and annotation for P. cinnamomi using a combination of Oxford Nanopore and Illumina sequencing technologies. The annotation was done using RNA-Seq data as supporting gene evidence. The final assembly consisted of 133 scaffolds, with an estimated genome size of 109.7 Mb, N50 of 1.18 Mb, and BUSCO completeness score of 97.5%. Genome partitioning analysis revealed that P. cinnamomi has a two-speed genome characteristic, similar to that of other oomycetes and fungal plant pathogens. In planta gene expression analysis revealed up-regulation of pathogenicity-related genes, suggesting their important roles during infection and host degradation. Conclusion This study has provided a high-quality reference genome and annotation for P. cinnamomi . This is among the best assembled genomes for any Phytophthora species assembled to date and thus resulted in improved identification and characterization of pathogenicity-related genes, some of which were undetected in previous versions of genome assemblies. Phytophthora cinnamomi harbours a large number of effector genes which are located in the gene-poor regions of the genome. This unique genomic partitioning provides P. cinnamomi with a high level of adaptability and could contribute to its success as a highly invasive species. Finally, the genome sequence, its annotation and the pathogenicity effectors identified in this study will serve as an important resource that will enable future studies to better understand and mitigate the impact of this important pathogen.

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag are ill-defined. Here, we provided a comprehensive and comparative description of male liver circadian gene expression, encompassing transcriptomes, whole-cell proteomes and nuclear proteomes, under normal and after ECD conditions. Under both conditions, post-translation, rather than transcription, is the dominant contributor to circadian functional outputs. After ECD, post-transcriptional and post-translational processes are the major contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, ECD re-writes the rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome. The re-writing, which is associated with changes of circadian regulatory cis-elements, RNA-processing and protein localization, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery. Circadian gene expression is fundamental to the circadian clock. Here the author showed post-translational processing is the dominant contributor to circadian nuclear proteome and Environmental Circadian Disruption re-writes the entire gene expression process from transcription to post-translation.

Species of Armillaria are distributed globally and include some of the most important pathogens of forest and ornamental trees. Some of them form large long-living clones that are considered as one of the largest organisms on earth and are capable of long-range spore-mediated transfer as well as vegetative spread by drought-resistant hyphal cords called rhizomorphs. However, the virus community infecting these species has remained unknown. In this study we used dsRNA screening and high-throughput sequencing to search for possible virus infections in a collection of Armillaria isolates representing three diferent species: Armillaria mellea from South Africa, A. borealis from Finland and Russia (Siberia) and A. cepistipes from Finland. Our analysis revealed the presence of both negativesense RNA viruses and positive-sense RNA viruses, while no dsRNA viruses were detected. The viruses included putative new members of virus families Mymonaviridae, Botourmiaviridae and Virgaviridae and members of a recently discovered virus group tentatively named “ambiviruses” with ambisense bicistronic genomic organization. We demonstrated that Armillaria isolates can be cured of viruses by thermal treatment, which enables the examination of virus efects on host growth and phenotype using isogenic virus-infected and virus-free strains.

New data show that Clock–Bmal1, the central transcriptional activator that drives expression of circadian target genes, also recruits the Ddb1–Cullin-4 ubiquitin ligase to clock promoters to enhance the subsequent binding of the feedback repressors that generate the circadian periodicity of gene expression. Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock–Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock–Bmal1 activity. We found that mouse Clock–Bmal1 recruits the Ddb1–Cullin-4 ubiquitin ligase to Per ( Per1 and Per2 ), Cry ( Cry1 and Cry2 ) and other circadian target genes. Histone H2B monoubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1 and Cullin-4a. Depletion of Ddb1–Cullin-4a or an independent decrease in H2B monoubiquitination caused defective circadian feedback and decreased the association of the Per complex with DNA-bound Clock–Bmal1. Clock–Bmal1 thus covalently marks Per genes for subsequent recruitment of the Per complex. Our results reveal a chromatin-mediated signal from the positive to the negative limb of the clock that provides a licensing mechanism for circadian feedback.

Idiopathic pulmonary fibrosis (IPF) is a severe and progressive chronic fibrosing interstitial lung disease with causes that have remained unclear to date. Development of effective treatments will require elucidation of the detailed pathogenetic mechanisms of IPF at both the molecular and cellular levels. With a biomedical corpus that includes IPF-related entities and events, text-mining systems can efficiently extract such mechanism-related information from huge amounts of literature on the disease. A novel corpus consisting of 150 abstracts with 9297 entities intended for training a text-mining system was constructed to clarify IPF-related pathogenetic mechanisms. For this corpus, entity information was annotated, as were relation and event information. To construct IPF-related networks, we also conducted entity normalization with IDs assigned to entities. Thereby, we extracted the same entities, which are expressed differently. Moreover, IPF-related events have been defined in this corpus, in contrast to existing corpora. This corpus will be useful to extract IPF-related information from scientific texts. Because many entities and events are related to lung diseases, this freely available corpus can also be used to extract information related to other lung diseases such as lung cancer and interstitial pneumonia caused by COVID-19.