Tofacitinib in Refractory Scleritis: A Case Series.

Tofacitinib, a Janus kinase inhibitor, has been recently investigated as a potential therapy for refractory scleritis. Despite treatment with systemic immunosuppressive agents, scleritis is refractory to conventional therapy in a significant number of patients. Hereby, we report the use of tofacitinib as a steroid-sparing immunomodulatory agent in three patients with refractory scleritis who were either recalcitrant or intolerant to conventional therapy.

Evolution of pathogenicity-associated genes in Rhizoctonia solani AG1-IA by genome duplication and transposon-mediated gene function alterations.

BACKGROUND: Rhizoctonia solani is a polyphagous fungal pathogen that causes diseases in crops. The fungal strains are classified into anastomosis groups (AGs); however, genomic complexity, diversification into the AGs and the evolution of pathogenicity-associated genes remain poorly understood. RESULTS: We report a recent whole-genome duplication and sequential segmental duplications in AG1-IA strains of R. solani. Transposable element (TE) clusters have caused loss of synteny in the duplicated blocks and introduced differential structural alterations in the functional domains of several pathogenicity-associated paralogous gene pairs. We demonstrate that the TE-mediated structural variations in a glycosyl hydrolase domain and a GMC oxidoreductase domain in two paralogous pairs affect the pathogenicity of R. solani. Furthermore, to investigate the association of TEs with the natural selection and evolution of pathogenicity, we sequenced the genomes of forty-two rice field isolates of R. solani AG1-IA. The genomic regions with high population mutation rates and with the lowest nucleotide diversity are enriched with TEs. Genetic diversity analysis predicted the genes that are most likely under diversifying and purifying selections. We present evidence that a smaller variant of a glucosamine phosphate N-acetyltransferase (GNAT) protein, predicted to be under purifying selection, and an LPMP_AA9 domain-containing protein, predicted to be under diversifying selection, are important for the successful pathogenesis of R. solani in rice as well as tomato. CONCLUSIONS: Our study has unravelled whole-genome duplication, TE-mediated neofunctionalization of genes and evolution of pathogenicity traits in R. solani AG1-IA. The pathogenicity-associated genes identified during the study can serve as novel targets for disease control.

A rare case of atypical Cogan's syndrome presenting as encephalitis.

Cogan's syndrome (CS) is a rare autoimmune vasculitis of unknown aetiology characterised by non-syphilitic interstitial keratitis, audiovestibular symptoms, sometimes systemic symptoms, and multi-organ involvement. Atypical CS has other ocular features, such as scleritis, episcelritis, retinitis, and optic neuritis. Diagnosis of CS is purely clinical without a confirmatory test. Hereby, we report a case of atypical CS presenting with features of encephalitis who was treated successfully with intravenous pulse methylprednisolone with cyclophosphamide. It is important to consider CS in the differential diagnosis of encephalitis with ocular and vestibular symptoms in young patients, as high morbidity and mortality rates are effectively lowered by early immunosuppressive treatment.

Unusual Cause of Vision Loss in a Case of Lupus.

Lupus can affect vision in various ways, commonly due to vasculitic retinopathy, and can also result from ischemic optic neuropathy secondary to antiphospholipid syndrome. Anaemic retinopathy is most likely to occur in patients with severe anaemia or associated with thrombocytopenia. Causes of decreased visual acuity in anaemia include haemorrhages involving the macula, macular oedema, optic disc oedema and ischemic optic neuropathy. We herein describe an unusual cause of loss of vision in a lupus patient associated with severe anaemia and thrombocytopenia. Ocular examination was suggestive of anaemic retinopathy. Her vision improved with concomitant resolution of retinal findings in 1 month after treatment for lupus with anaemia correction. Hence, even though vision loss in lupus is dreadful, retinal changes in fundus examination should be carefully looked at to rule out anaemic retinopathy, as it is almost always reversible with correction of anaemia unlike lupus retinopathy.

Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors.

Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Here, we report that Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. RNase activity is prominent on NGJ1 as well as other bacterial RNA while DNase activity is pertinent to only other bacteria. The associated immunity (TsiTBg) proteins harbor non-canonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxin-antitoxin (TA) systems. Genome analysis reveals that homologs of TseTBg are either encoded as TA or T6SS effectors in diverse bacteria. Our results indicate that a new ORF (encoding a hypothetical protein) has evolved as a result of operonic fusion of TA type TseTBg homolog with certain T6SS-related genes by the action of IS3 transposable elements. This has potentially led to the conversion of a TA into T6SS effector in Burkholderia. Our study exemplifies that bacteria can recruit toxins of TA systems as T6SS weapons to diversify its arsenal to dominate during inter-bacterial competitions.

RS_CRZ1, a C2H2-Type Transcription Factor Is Required for Pathogenesis of Rhizoctonia solani AG1-IA in Tomato.

Rhizoctonia solani is a necrotrophic fungal pathogen that causes disease in diverse plant species. In recent years, the genomic and transcriptomic studies have identified several candidate pathogenicity determinants of R. solani; however, most of them remain to be validated. In this study, we report a viral vector-based host-induced gene silencing (HIGS) as well as a dsRNA (double-stranded RNA)-based approach to effectively downregulate genes of R. solani AG1-IA (BRS1 strain) during pathogenesis in tomato. We tested a few of the in-planta upregulated R. solani genes and observed that silencing of one of them, i.e., RS_CRZ1 (a C2H2 type zinc finger transcription factor) significantly compromises the pathogenesis of R. solani in tomato. The RS_CRZ1-silenced plants not only exhibited significant reduction in disease symptoms, but the depth of pathogen colonization was also compromised. Furthermore, we identified the R. solani genes that were coregulated with RS_CRZ1 during the pathogenicity process. The HIGS-mediated silencing of a few of them [CL1756Contig1; subtilisin-like protease and CL1817Contig2; 2OG-Fe(II) oxygenase] compromised the pathogenesis of R. solani in tomato. The ectopic expression of RS_CRZ1 complemented the crz1 mutant of yeast and restored tolerance against various metal ion stress. Overall, our study reveals the importance of RS_CRZ1 in managing the hostile environment encountered during host colonization. Also, it emphasizes the relevance of the HIGS and dsRNA-based gene silencing approach toward functional characterization of pathogenicity determinants of R. solani.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Fungal effectors, the double edge sword of phytopathogens.

Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from the host and to colonize upon them. They deploy various proteinaceous as well as non-proteinaceous secreted molecules commonly referred as effectors to sabotage host machinery during the infection process. The effectors are important virulence determinants of pathogenic fungi and play important role in successful pathogenesis, predominantly by avoiding host-surveillance system. However, besides being important for pathogenesis, the fungal effectors end-up being recognized by the resistant cultivars of the host, which mount a strong immune response to ward-off pathogens. Various recent studies involving different pathosystem have revealed the virulence/avirulence functions of fungal effectors and their involvement in governing the outcome of host-pathogen interactions. However, the effectors and their cognate resistance gene in the host remain elusive for several economically important fungal pathogens. In this review, using examples from some of the biotrophic, hemi-biotrophic and necrotrophic pathogens, we elaborate the double-edged functions of fungal effectors. We emphasize that knowledge of effector functions can be helpful in effective management of fungal diseases in crop plants.