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Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.

Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties.

Background Theory predicts that dependency within host-endosymbiont interactions results in endosymbiont genome size reduction. Unexpectedly, the largest Wolbachia genome was found in the obligate, parthenogenesis-associated w Fol. In this study, we investigate possible processes underlying this genome expansion by comparing a re-annotated w Fol genome to other Wolbachia genomes. In addition, we also search for candidate genes related to parthenogenesis induction (PI). Results Within w Fol, we found five phage WO regions representing 25.4% of the complete genome, few pseudogenized genes, and an expansion of DNA-repair genes in comparison to other Wolbachia . These signs of genome conservation were mirrored in the w Fol host, the springtail F. candida , which also had an expanded DNA-repair gene family and many horizontally transferred genes. Across all Wolbachia genomes, there was a strong correlation between gene numbers of Wolbachia strains and their hosts. In order to identify genes with a potential link to PI, we assembled the genome of an additional PI strain, w Lcla. Comparisons between four PI Wolbachia, including w Fol and w Lcla, and fourteen non-PI Wolbachia yielded a small set of potential candidate genes for further investigation. Conclusions The strong similarities in genome content of w Fol and its host, as well as the correlation between host and Wolbachia gene numbers suggest that there may be some form of convergent evolution between endosymbiont and host genomes. If such convergent evolution would be strong enough to overcome the evolutionary forces causing genome reduction, it would enable expanded genomes within long-term obligate endosymbionts.

Potato late blight, caused by the destructive Irish famine pathogen Phytophthora infestans , is a major threat to global food security 1 , 2 . All late blight resistance genes identified to date belong to the coiled-coil, nucleotide-binding, leucine-rich repeat class of intracellular immune receptors 3 . However, virulent races of the pathogen quickly evolved to evade recognition by these cytoplasmic immune receptors 4 . Here we demonstrate that the receptor-like protein ELR (elicitin response) from the wild potato Solanum microdontum mediates extracellular recognition of the elicitin domain, a molecular pattern that is conserved in Phytophthora species. ELR associates with the immune co-receptor BAK1/SERK3 and mediates broad-spectrum recognition of elicitin proteins from several Phytophthora species, including four diverse elicitins from P. infestans . Transfer of ELR into cultivated potato resulted in enhanced resistance to P. infestans . Pyramiding cell surface pattern recognition receptors with intracellular immune receptors could maximize the potential of generating a broader and potentially more durable resistance to this devastating plant pathogen. A gene that helps protect potatoes from destructive late blight is identified in a wild relative. It encodes a membrane receptor-like protein, the first discovered in this system, and makes cultivated potato plants more resistant to a broad range of pathogens.

Anaerobic ammonium-oxidizing (anammox) bacteria are a group of strictly anaerobic chemolithoautotrophic microorganisms. They are capable of oxidizing ammonium to nitrogen gas using nitrite as a terminal electron acceptor, thereby facilitating the release of fixed nitrogen into the atmosphere. The anammox process is thought to exert a profound impact on the global nitrogen cycle and has been harnessed as an environment-friendly method for nitrogen removal from wastewater. In this study, we present the first closed genome sequence of an anammox bacterium, Kuenenia stuttgartiensis MBR1. It was obtained through Single-Molecule Real-Time (SMRT) sequencing of an enrichment culture constituting a mixture of at least two highly similar Kuenenia strains. The genome of the novel MBR1 strain is different from the previously reported Kuenenia KUST reference genome as it contains numerous structural variations and unique genomic regions. We find new proteins, such as a type 3b (sulf)hydrogenase and an additional copy of the hydrazine synthase gene cluster. Moreover, multiple copies of ammonium transporters and proteins regulating nitrogen uptake were identified, suggesting functional differences in metabolism. This assembly, including the genome-wide methylation profile, provides a new foundation for comparative and functional studies aiming to elucidate the biochemical and metabolic processes of these organisms.

Ulcerative oral mucositis and infection are frequent complications in hematopoietic stem cell transplant (HSCT) recipients. The aim of this study was to investigate the relationship between oral ulcerations and HSV-1, EBV and CMV excretion and the presence of aciclovir-resistant HSV-1 strains in HSCT recipients. This prospective observational study included 49 adult patients who underwent allogeneic HSCT. In total, 26 patients received myeloablative and 23 received non-myeloablative conditioning. Ulcerations on non-keratinized and keratinized oral mucosa were scored and oral rinsing samples were taken twice weekly. Viral loads were determined by real-time PCR. Samples from patients remaining HSV-1 positive despite antiviral treatment were studied for resistance to antivirals. Having an HSV-1 or EBV DNA–positive sample was a significant predictor for ulceration of keratinized mucosa. HSV-1 was a significant predictor for ulcerations on non-keratinized mucosa as well. Persistent HSV-1 infection occurred in 12 of 28 patients treated with antiviral medication and aciclovir-resistant HSV-1 was found in 5 persistent infections. In conclusion, HSV-1 is a predictor of ulcerations on non-keratinized as well as keratinized oral mucosa following HSCT. The role of EBV deserves further study. Persistent HSV-1 replication despite antiviral treatment is common and is due to resistance in 18% of treated patients.

Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2 , respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed . Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation.

Congenital cytomegalovirus infection (cCMV) may lead to symptoms at birth and long-term consequences. We present a nationwide, retrospective cohort study on the outcome of cCMV up to age 6 years. For this study we identified cCMV, using polymerase chain reaction, by analysing dried blood spots, which are taken shortly after birth for neonatal screening. The group of children with cCMV were compared to a group of children who were cCMV negative at birth. Data were collected about their health and development up to age 6 years. Parents of 73 693 children were invited to participate, and 32 486 (44·1%) gave informed consent for testing of their child's dried blood spot for CMV. Of the 31 484 dried blood spots tested, 156 (0·5%) were positive for cCMV. Of these, four (2·6%) children had been diagnosed with cCMV prior to this study. This unique retrospective nationwide study permits the estimation of long-term sequelae of cCMV up to the age of 6 years. The birth prevalence of cCMV in this study was 0·5%, which is in line with prior estimates. Most (97·4%) children with cCMV had not been diagnosed earlier, indicating under-diagnosis of cCMV.

Research on diploid hybrid potato has made fast advances in recent years. In this review we give an overview of the most recent and relevant research outcomes. We define different components needed for a complete hybrid program: inbred line development, hybrid evaluation, cropping systems and variety registration. For each of these components the important research results are discussed and the outcomes and issues that merit further study are identified. We connect fundamental and applied research to application in a breeding program, based on the experiences at the breeding company Solynta. In the concluding remarks, we set hybrid breeding in a societal perspective, and we identify bottlenecks that need to be overcome to allow successful adoption of hybrid potato.

Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn’s disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By surveying 12,791 gut metagenomes, we recapitulated known associations with metabolic diseases and inflammatory bowel disease. We uncovered a higher prevalence and abundance of R. gnavus in Westernized populations and observed bacterial relative abundances up to 83% in newborns. Next, we built a resource of R. gnavus isolates (N = 45) from healthy individuals and Crohn’s disease patients and generated complete R. gnavus genomes using PacBio circular consensus sequencing. Analysis of these genomes and publicly available high-quality draft genomes (N = 333 genomes) revealed multiple clades which separated Crohn’s-derived isolates from healthy-derived isolates. Presumed R. gnavus virulence factors could not explain this separation. Bacterial genome-wide association study revealed that Crohn’s-derived isolates were enriched in genes related to mobile elements and mucin foraging. Together, we present a large R. gnavus resource that will be available to the scientific community and provide novel biological insights into the global distribution and genomic variation of R. gnavus . Here, the authors present a global meta-analysis of the human gut bacterium Ruminococcus gnavus , established an isolate collection with complete genomes and identified genetic features correlating with geography, age and disease using newly generated and public genome data.