A TNIP1-driven systemic autoimmune disorder with elevated IgG4.

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333P variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88. The variant increased interferon-ß without altering nuclear factor kappa-light-chain-enhancer of activated B cells signaling, and impaired MyD88 and IRAK1 recruitment to autophagosomes. Additionally, the Q333P variant impaired TNIP1 localization to damaged mitochondria and mitophagosome formation. Damaged mitochondria were abundant in the salivary epithelial cells of Tnip1Q346P mice. These findings suggest that TNIP1-mediated autoimmunity may be a consequence of increased TLR7 signaling due to impaired recruitment of downstream signaling molecules and damaged mitochondria to autophagosomes and may thus respond to TLR7-targeted therapeutics.

Monocytes asphyxiate germinal centers.

Some bacteria and parasites, such as Salmonella, actively disrupt germinal centers and elicit only low affinity antibodies, but the mechanisms by which microbes alter these responses is poorly understood. In this issue of Immunity, Biram et al. (2022) uncover a mechanism by which Salmonella recruits Sca-1+ monocytes to germinal centers and impairs metabolic adaptation.

TLR7 gain-of-function genetic variation causes human lupus.

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1-7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10-12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP10-12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

Cytoplasmic HYL1 modulates miRNA-mediated translational repression.

MicroRNAs (miRNAs) control various biological processes by repressing target mRNAs. In plants, miRNAs mediate target gene repression via both mRNA cleavage and translational repression. However, the mechanism underlying this translational repression is poorly understood. Here, we found that Arabidopsis thaliana HYPONASTIC LEAVES1 (HYL1), a core component of the miRNA processing machinery, regulates miRNA-mediated mRNA translation but not miRNA biogenesis when it localized in the cytoplasm. Cytoplasmic HYL1 localizes to the endoplasmic reticulum and associates with ARGONAUTE1 (AGO1) and ALTERED MERISTEM PROGRAM1. In the cytoplasm, HYL1 monitors the distribution of AGO1 onto polysomes, binds to the mRNAs of target genes, represses their translation, and partially rescues the phenotype of the hyl1 null mutant. This study uncovered another function of HYL1 and provides insight into the mechanism of plant gene regulation.

Multiomics analysis reveals a link between Brassica-specific miR1885 and rapeseed tolerance to low temperature.

Brassica crops include various edible vegetable and plant oil crops, and their production is limited by low temperature beyond their tolerant capability. The key regulators of low-temperature resistance in Brassica remain largely unexplored. To identify posttranscriptional regulators of plant response to low temperature, we performed small RNA profiling, and found that 16 known miRNAs responded to cold treatment in Brassica rapa. The cold response of seven of those miRNAs were further confirmed by qRT-PCR and/or northern blot analyses. In parallel, a genome-wide association study of 220 accessions of Brassica napus identified four candidate MIRNA genes, all of which were cold-responsive, at the loci associated with low-temperature resistance. Specifically, these large-scale data analyses revealed a link between miR1885 and the plant response to low temperature in both B. rapa and B. napus. Using 5' rapid amplification of cDNA ends approach, we validated that miR1885 can cleave its putative target gene transcripts, Bn.TIR.A09 and Bn.TNL.A03, in B. napus. Furthermore, overexpression of miR1885 in Semiwinter type B. napus decreased the mRNA abundance of Bn.TIR.A09 and Bn.TNL.A03 and resulted in increased sensitivity to low temperature. Knocking down of miR1885 in Spring type B. napus led to increased mRNA abundance of its targets and improved rapeseed tolerance to low temperature. Together, our results suggested that the loci of miR1885 and its targets could be potential candidates for the molecular breeding of low temperature-tolerant Spring type Brassica crops.

Dataset artificial augmentation with a small number of training samples for reflectance estimation.

The accuracy of the spectral reflectance estimation approaches highly depends on the amount, coverage, and representation of valid samples in the training dataset. We present a dataset artificial augmentation approach with a small number of actual training samples by light source spectra tuning. Then, the reflectance estimation process is carried out with our augmented color samples for commonly used datasets (IES, Munsell, Macbeth, Leeds). Finally, the impact of the augmented color sample number is investigated using different augmented color sample numbers. The results show that our proposed approach can artificially augment the color samples from CCSG 140 color samples to 13791 color samples and even more. The reflectance estimation performances with augmented color samples are much higher than with the benchmark CCSG datasets for all tested datasets (IES, Munsell, Macbeth, Leeds, as well as a real-scene hyperspectral reflectance database). It indicates that the proposed dataset augmentation approach is practical for improving the reflectance estimation performances.

Species-specific arsenic species and health risk assessment in seaweeds from tropic coasts of South China Sea.

Arsenic (As) is a notorious toxic contamination in marine environments, while the toxicity and health risk of As is highly dependent on As species in seafoods. In this study, we hypothesized that the species-specific As bioaccumulation and species resulted in species-specific healthy risk of As in seaweeds. To test the hypothesis, we collected 10 common edible seaweeds from the coast of Hainan Island in South China Sea. Then we comparatively quantified concentration of total As and 5 major As species [AsB, DMA, MMA, As(III), and As(V)] in seaweeds. The results revealed that the concentrations of total As varied significantly among 10 seaweed species. Specially, the highest total As concentration were found in brown seaweeds, followed by red seaweeds, and green seaweeds. Furthermore, the percentage of 5 As species to total As differed significantly among 10 seaweeds. The percentage of AsB was highest in Caulerpa lentillifera (53%) and lowest in Sargassum oligocystum (13%), while that of As(V) was lowest in Caulerpa lentillifera (21%) and highest in Sargassum oligocystum (81%). The iAs [As(III) + As(V)] exhibited highest value in brown seaweeds and least value in green seaweeds. The potential human health risk assessment indicated that the consumption of brown seaweeds of Sargassum oligocystum and Sargassum polycystum could cause a considerable carcinogenic risk and non-carcinogenic risk to residents. Overall, our findings here largely validated our hypothesis that the species-specific As bioaccumulation and As species had great significance to healthy risk of As in seaweeds.

Differential Analysis of Three Copper-Based Nanomaterials with Different Morphologies to Suppress Alternaria alternata and Safety Evaluation.

The overuse of copper-based fertilizers and pesticides over the last few decades has resulted in detrimental risks to our environment. Nano-enabled agrichemicals with a high effective utilization ratio have shown great potential for maintaining or minimizing environmental issues in agriculture. Copper-based nanomaterials (Cu-based NMs) serve as a promising alternative to fungicides. Three types of Cu-based NMs with different morphologies were analyzed for their different antifungal effects on Alternaria alternata in this current study. Compared to commercial copper hydroxide water power (Cu(OH)2 WP), all tested Cu-based NMs, including cuprous oxide nanoparticles (Cu2O NPs), copper nanorods (Cu NRs) and copper nanowires (Cu NWs), especially Cu2O NPs and Cu NWs, showed higher antifungal activity against Alternaria alternata. Its EC50 were 104.24 and 89.40 mg L-1, respectively, achieving comparable activity using a dose approximately 1.6 and 1.9-fold lower. Cu-based NMs could introduce the downregulation of melanin production and soluble protein content. In contrast to trends in antifungal activity, Cu2O NPs showed the strongest power in regulating melanin production and protein content and similarly exhibited the highest acute toxicity to adult zebrafish compared to other Cu-based NMs. These results demonstrate that Cu-based NMs could offer great potential in plant disease management strategies.

MicroRNA319a regulates plant resistance to Sclerotinia stem rot.

MicroRNA319a (miR319a) controls cell division arrest in plant leaves by inhibiting the expression of TCP (TEOSINTE BRANCHED 1/CYCLOIDEA/PCF) family genes. However, it is unclear whether miR319a influences infection by necrotrophic pathogens and host susceptibility. In this study, we revealed that miR319a affects plant resistance to stem rot disease caused by Sclerotinia sclerotiorum. In Brassica rapa plants infected with S. sclerotiorum, miR319a levels increased while the expression levels of several BraTCP genes significantly decreased compared with those of uninfected plants. Overexpression of BraMIR319a in B. rapa increased the susceptibility of the plants to S. sclerotiorum and aggravated stem rot disease, whereas overexpression of BraTCP4-1 promoted plant resistance. RNA sequencing data revealed a potential relationship between miR319a and pathogen-related WRKY genes. Chromatin immunoprecipitation, electrophoretic mobility shift, and reporter transaction assays showed that BraTCP4-1 could bind to the promoters of WRKY75, WRKY70, and WRKY33 and directly activate these pathogen-related genes. Moreover, the expression levels of WRKY75, WRKY70, and WRKY33 in plants overexpressing BraMIR319a decreased significantly, whereas those of plants overexpressing BraTCP4-1 increased significantly, relative to the wild type. These results suggest that miR319a and its target gene BraTCP4 control stem rot resistance through pathways of WRKY genes.

MicroRNA166 Monitors SPOROCYTELESS/NOZZLE for Building of the Anther Internal Boundary.

The internal boundary between inner and outer microsporangia within anthers is essential for male fertility of vascular plants. Dehiscence zones embedded in the boundary release pollen for fertilization. However, the molecular mechanism underlying boundary formation in anthers remains poorly understood. Here, we report that microRNA166 (miR166) and its target PHABULOSA (PHB) regulate SPOROCYTELESS/NOZZLE (SPL/NZZ), which controls microsporogenesis. In developing anthers of Arabidopsis (Arabidopsis thaliana), the expression domains of miR165/6 and SPL/NZZ are overlapped and rearranged synchronously. Dominant mutation of PHB suppresses SPL/NZZ expression on the adaxial sides of stamens, resulting in a thickened boundary, whereas activation of MIR166g up-regulates SPL/NZZ expression, leading to ectopic microsporogenesis in the boundary. PHB limits the expression domains of SPL/NZZ to facilitate construction of the boundary, while miR166 preserves the expression domains of SPL/NZZ by inhibiting PHB to allow the inner microsporangia to take shape. Subsequently, PHB activates the key stem cell maintainer WUSCHEL in anthers to restrict the stomium cells to the boundary so that dehiscence zones develop and release pollen properly. These findings link adaxial/abaxial polarity to microsporogenesis in building of the internal boundary of anthers and thus advance the concepts underlying the establishment of the internal structure of male organs.