The TSN1 Binding Protein RH31 Is a Component of Stress Granules and Participates in Regulation of Salt-Stress Tolerance in Arabidopsis

Tudor staphylococcal nucleases (TSNs) are evolutionarily conserved RNA binding proteins, which include redundant TSN1 and TSN2 in Arabidopsis. It has been showed TSNs are the components of stress granules (SGs) and regulate plant growth under salt stress. In this study, we find a binding protein of TSN1, RH31, which is a DEAD-box RNA helicase (RH). Subcellular localization studies show that RH31 is mainly located in the nucleus, but under salinity, it translocates to the cytoplasm where it accumulates in cytoplasmic granules. After cycloheximide (CHX) treatment which can block the formation of SGs by interfering with mRNP homeostasis, these cytoplasmic granules disappeared. More importantly, RH31 co-localizes with SGs marker protein RBP47. RH31 deletion results in salt-hypersensitive phenotype, while RH31 overexpression causes more resistant to salt stress. In summary, we demonstrate that RH31, the TSN1 binding protein, is a component of plant SGs and participates in regulation of salt-stress tolerance in Arabidopsis.

ANCA-Associated Vasculitis Following Johnson and Johnson COVID-19 Vaccine

Antineutrophil cytoplasmic autoantibodies associated vasculitis(AAV) is characterized by antibodies against antigens in cytoplasmic granules of neutrophils and predominantly affects small vessels. AAV after COVID-19 mRNA vaccination has been reported. We report rare case of AAV in a patient who presented with rapidly progressive glomerulonephritis(RPGN) after Johnson & Johnson vaccine administration.

Selective autophagic receptor NbNBR1 prevents NbRFP1-mediated UPS-dependent degradation of βC1 to promote geminivirus infection

Autophagy is an evolutionarily conserved, lysosomal/vacuolar degradation mechanism that targets cell organelles and macromolecules. Autophagy and autophagy-related genes have been studied for their antiviral and pro-viral roles in virus-infected plants. Here, we demonstrate the pro-viral role of a selective autophagic receptor NbNBR1 in geminivirus-infected Nicotiana benthamiana plants. The βC1 protein encoded by tomato yellow leaf curl China betasatellite (TYLCCNB) that is associated with tomato yellow leaf curl China virus (TYLCCNV) enhanced the expression level of NbNBR1. Then NbNBR1 interacted with βC1 to form cytoplasmic granules. Interaction of NbNBR1 with βC1 could prevent degradation of βC1 by the NbRFP1, an E3 ligase. Overexpression of NbNBR1 in N. benthamiana plants increased βC1 accumulation and promoted virus infection. In contrast, silencing or knocking out NbNBR1 expression in N. benthamiana suppressed βC1 accumulation and inhibited virus infection. A single amino acid substitution in βC1 (βC1K4A) abolished its interaction with NbNBR1, leading to a reduced level of βC1K4A. The TYLCCNV/TYLCCNBK4A mutant virus caused milder disease symptoms and accumulated much less viral genomic DNAs in the infected plants. Collectively, the results presented here show how a viral satellite-encoded protein hijacks host autophagic receptor NbNBR1 to form cytoplasmic granules to protect itself from NbRFP1-mediated degradation and facilitate viral infection.

ultrastrutal investigation on Pseudo Chediak–Higashi abnormality in acute lymphoblastic leukemia: A case report

Pseudo Chediak-Higashi (PCH) granules are mainly common in acute myeloid leukemia. Here we found a patient diagnosed with common-B acute lymphoblastic leukemia(ALL) with PCH cytoplasmic granules, which was rarely seen in daily diagnosis. The morphology of the granules is different in transmission electron microscope (TEM) from cases reported before. There is a vesicle with various-sized particles surrounding the nucleus, in addition to the particles, a multiple-layer membrane structure was also detected in the vesicle.

Comparative Analysis Of Orthologous Mast Cell Chymases Active Sites Using Bioinformatics Tools

Mast cells, neutrophils, basophils, natural killer cells, and cytotoxic T cells are among the hematopoietic cell lines originating from immune cells. The importance of mammalian mast cells in innate immunity has piqued the scientific community's interest. cytoplasmic granules of mast cells. Histamine, proteoglycans, proteins, and cytokines are examples of compounds (mediators) that produce mast cell cytoplasmic granules. When external stimuli are received, these granules are released, causing degranulation. Mast cells generate a lot of proteases including chymase, tryptase, and type A carboxypeptidase, among other things. The structure of chymase cma1 was unknown in mice, but it shares 74 percent of its human sequence with chymase CMA1, which was used as a reference. The human CMA1 structure was used to establish and interpret the mouse cma1 structure. Significant residues from the active site, such as catalytic triads and binding residues, were examined. The position of a catalytic triad in human CMA1 chymase and mouse cma1 chymase has been discovered to be similar. Val 175 and Val 197, respectively, replaced two Ala 192 and Gly 214 residues in active site binding residues in target, according to active site residue analysis. We may deduce from this substitution that the cleavage specificity of mouse cma1 chymase varies from that of human CMA1 chymase.

Metastatic melanoma in a Saanen goat: clinical, ultrasonographic and anatomopathological aspects - case report

ABSTRACT This report describes clinical, ultrasonographic and anatomopathological findings in a case of metastatic melanoma in an adult Saanen goat. Clinically, the goat had apathy, an intra-abdominal palpable firm structure, and exophytic keratinized areas on the skin of the udder. Ultrasound revealed non-encapsulated oval structures, with heterogeneous echogenicity and marked central and peripheral vascularization, and hypoechoic hepatic multifocal to coalescent areas. In the udder, there were non-encapsulated oval structures with heterogeneous echogenicity and hyperechoic center surrounded by hypoechogenic tissue. Grossly, there were black multifocal to coalescent areas in the liver, as well as black nodules in mammary and mesenteric lymph nodes, uterus, spleen, and myocardium. Microscopically, multifocal melanocytic neoplastic proliferation was observed in the dermis and junction of the udder epidermis. Most of the neoplastic cells had cytoplasmic granules of melanin. In the liver there were areas of neoplastic tissue compressing the adjacent parenchyma, with central foci of necrosis, mild desmoplasia, and multifocal infiltration of malignant cells into the adjacent tissues. Similar findings were observed in the mammary and mesenteric lymph nodes, uterus, spleen, and myocardium, which characterized metastatic melanoma. Ultrasonography played a key role for establishing the diagnosis of a metastatic melanoma and helped establish a proper clinical management protocol.

Cellular toxicity of iHAP1 and DT-061 does not occur through PP2A-B56 targeting

PP2A is an abundant phosphoprotein phosphatase that acts as a tumor suppressor. For this reason, compounds able to activate PP2A are attractive anticancer agents. The small molecule compounds iHAP1 and DT-061 have recently been reported by Leonard et al. (2020) and Morita et al. (2020) in Cell to selectively stabilize specific PP2A-B56 complexes to mediate cell killing. Here, we show that this is not the case and question key findings in these papers. Through genome wide CRISPR-Cas9 screens, we establish the biological pathways targeted by these compounds. We find that iHAP1 directly targets microtubule assembly both in vitro and in vivo and thus works as a microtubule poison. In contrast, DT-061 disrupts both the Golgi apparatus and the endoplasmic reticulum and we directly visualize DT-061 in cytoplasmic granules that co-localize with Golgi markers. Our work argues that iHAP1 and DT-061 cannot be used for dissecting PP2A-B56 biology.

Biochemical and subcellular characterization of a squid hnRNPA/B-like protein in osmotic stress activated cells reflects molecular properties conserved in this protein family

In previous works, we characterized a novel, strongly basic, squid hnRNPA/B-like Protein 2 in presynaptic terminals of squid neurons. Here, we show that squid hnRNPA/B-like Protein 2 are exclusively nuclear localization and relocated to cytoplasmic granules containing hnRNPA1 and Poly-A binding protein-1 (PABP-1) when the cells are treated with sorbitol. Also, we show an interaction of hnRNPA/B like Protein 2 with squid RNA, its interfered with dynamic of formation of hnRNPA/B like Protein 2 dimers, whereas possibly involved disulfide bounds and postranslations modification in a distinct stage of dimers formation. An understanding of the molecular and biochemical mechanisms involved in the stability of the dimeric form, and the regulation of the transition between monomeric and dimeric forms may bring insights into evolution of several neurodegenerative diseases.

Early germline differentiation in bivalves: TDRD7 as a candidate investigational unit for Ruditapes philippinarum germ granule assembly

The germline is a key feature of sexual animals and the ways in which it separates from the soma differ widely across Metazoa. However, at least at some point during germline differentiation, some cytoplasmic supramolecular structures (collectively called germ plasm-related structures) are present and involved in its specification and/or differentiation. The factors involved in the assembly of these granular structures are various and non-ubiquitous among animals, even if some functional patterns and the presence of certain domains appear to be shared among some. For instance, the LOTUS domain is shared by Oskar, the Holometabola germ plasm master regulator, and some Tudor-family proteins assessed as being involved in the proper assembly of germ granules of different animals. Here, we looked for the presence of LOTUS-containing proteins in the transcriptome of Ruditapes philippinarum (Bivalvia). Such species is of particular interest because it displays annual renewal of gonads, sided by the renewal of germline differentiation pathways. Moreover, previous works have identified in its early germ cells cytoplasmic granules containing germline determinants. We selected the orthologue of TDRD7 as a candidate involved in the early steps of germline differentiation through bioinformatic predictions and immunohistological patterning (immunohistochemistry and immunofluorescence). We observed the expression of the protein in putative precursors of germline cells, upstream to the germline marker Vasa. This, added to the fact that orthologues of this protein are involved in the assembly of germ granules in mouse, zebrafish, and fly, makes it a worthy study unit for investigations on the formation of such structures in bivalves.