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Filamentous plant pathogens deliver effector proteins into host cells to suppress host defence responses and manipulate metabolic processes to support colonization. Understanding the evolution and molecular function of these effectors provides knowledge about pathogenesis and can suggest novel strategies to reduce damage caused by pathogens. However, effector proteins are highly variable, share weak sequence similarity and, although they can be grouped according to their structure, only a few structurally conserved effector families have been functionally characterized to date. Here, we demonstrate that Zinc-finger fold (ZiF) secreted proteins form a functionally diverse effector family in the blast fungus Magnaporthe oryzae. This family relies on the Zinc-finger motif for protein stability and is ubiquitously present in blast fungus lineages infecting 13 different host species, forming different effector tribes. Homologs of the canonical ZiF effector, AVR-Pii, from rice infecting isolates are present in multiple M. oryzae lineages. Wheat infecting strains of the fungus also possess an AVR-Pii like allele that binds host Exo70 proteins and activates the immune receptor Pii. Furthermore, ZiF tribes may vary in the proteins they bind to, indicating functional diversification and an intricate effector/host interactome. Altogether, we uncovered a new effector family with a common protein fold that has functionally diversified in lineages of M. oryzae. This work expands our understanding of the diversity of M. oryzae effectors, the molecular basis of plant pathogenesis and may ultimately facilitate the development of new sources for pathogen resistance. Author summary: Diseases caused by filamentous plant pathogens impact global food production, leading to severe economic and humanitarian consequences. These pathogens secrete hundreds of effectors inside the host to alter cellular processes and to promote infection and disease. Effector proteins have weak or no sequence similarity but can be grouped in structural families based on conserved protein folds. However, very few conserved effector families have been functionally characterized. We have identified a family of effectors with a shared Zinc-finger protein fold (ZiF) that is present in lineages of the blast fungus Magnaporthe oryzae that can, collectively, infect 13 different grasses. We characterized the binding of a sub-set of these proteins to putative Exo70 host targets and showed they can be recognized by the plant immune system. Furthermore, we show that other ZiF effectors do not bind Exo70 targets, suggesting functional specialization within this effector family for alternative interactors. These findings shed light on the diversity of effectors and their molecular functions, as well as potentially leading to the development of new sources of blast disease resistance. [ABSTRACT FROM AUTHOR]

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA‐binding protein of 43 kDa (TDP‐43) accumulation. Here we report the autopsy findings of a 64‐year‐old right‐handed man with an atypical TDP‐43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti‐phosphorylated TDP‐43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl‐insoluble fractions showed hyperphosphorylated TDP‐43 bands at 45 kDa and phosphorylated C‐terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP‐43 subtype and therefore may represent a new FTLD‐TDP phenotype. [ABSTRACT FROM AUTHOR]