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The impacts of climate change on worldwide crop production become increasingly severe. Thus, sustainable enhancements of agricultural production are needed. The present study investigated the effects of drought and arbuscular mycorrhizal fungi on wheat plants (Triticum aestivum) and their interaction with aphids. Considering predicted climate change scenarios, wheat plants were exposed to well‐watered conditions, continuous drought (CD), or pulsed (PD) drought and plants were grown without (NM) or with mycorrhizal (AM) fungi. Ear biomass and harvest index were evaluated when grains were produced. Moreover, drought‐ and mycorrhiza‐induced changes in the amino acid composition of leaf phloem exudates were studied and the population growth and survival of Sitobion avenae aphids on those plants measured. Wheat plants responded differently toward the irrigation treatments. Under drought stress, ear biomass was reduced, while AM resulted in an enhanced harvest index. In phloem exudates especially, relative concentrations of the osmoprotectant proline were modulated by drought. Aphid population size was influenced by the interaction of drought and mycorrhiza treatment. This study emphasizes the pronounced influence of irrigation frequency on plant performance and indicates positive contributions of AM that may be relevant for agriculture., Wheat plants were exposed to different irrigation regimes, and the effects of arbuscular mycorrhiza (AM) on plant and aphid performance were tested. For plants experiencing continuous or pulsed drought, AM had a growth‐promoting effect. Aphids had a poorer survival on those plants, indicating positive effects of AM in agriculture.

T-cells play a crucial role in progression of autoimmunity, including vitiligo, yet the initial steps triggering their activation and tissue damage remain unknown. Here we demonstrate increased presence of type-1 innate lymphoid cells (NK and ILC1)-producing interferon gamma (IFNγ) in the blood and in non-lesional skin of vitiligo patients. Melanocytes of vitiligo patients have strong basal expression of chemokine-receptor-3 (CXCR3) isoform B which is directly regulated by IFNγ. CXCR3B activation by CXCL10 at the surface of cultured human melanocytes induces their apoptosis. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T-cell proliferation and subsequent anti-melanocytic immunity. Inhibiting the CXCR3B activation prevents this apoptosis and the further activation of T cells. Our results emphasize the key role of CXCR3B in apoptosis of melanocytes and identify CXCR3B as a potential target to prevent and to treat vitiligo by acting at the early stages of melanocyte destruction., Tissue signals that prime autoreactive T cells at the onset of autoimmunity remain enigmatic. Here the authors show NK and ILC1 cells are increased in vitiligo patients, and induce melanocyte apoptosis via CXCR3B, which in turn leads to increased priming of T cell responses in cell culture.

Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents a major global cause of hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most of cases, do not eliminate viral genome that persists as a DNA episome in the nucleus of hepatocytes and constitutes a stable template for the continuous expression of viral genes. Several studies suggest that, among viral factors, the HBV core protein (HBc), well-known for its structural role in the cytoplasm, could have critical regulatory functions in the nucleus of infected hepatocytes. To elucidate these functions, we performed a proteomic analysis of HBc-interacting host-factors in the nucleus of differentiated human hepatocytes. The HBc interactome was found to consist primarily of RNA-binding proteins (RBPs), which are involved in various aspects of mRNA metabolism. Among them, we focused our studies on SRSF10, a RBP that was previously shown to regulate alternative splicing in a phosphorylation-dependent manner and to control stress and DNA damage responses, as well as viral replication. Functional studies combining SRSF10 knockdown and a pharmacological inhibitor of SRSF10 phosphorylation (1C8) showed that SRSF10 behaves as a restriction factor that regulates HBV RNAs levels and that its dephosphorylated form is likely responsible for the anti-viral effect. Surprisingly, neither SRSF10 knock-down nor 1C8 treatment modified the splicing of HBV RNAs but rather modulated the level of nascent HBV RNA. Altogether, our work suggests that in the nucleus of infected cells HBc interacts with multiple RBPs that regulate viral RNA metabolism. Our identification of SRSF10 as a new anti-HBV restriction factor offers new perspectives for the development of new host-targeted antiviral strategies.Author SummaryChronic infection with Hepatitis B virus (HBV) affects more than 250 millions of people world-wide and is a major global cause of liver cancer. Current treatments lead to a significant reduction of viremia in patients. However, viral clearance is rarely obtained and the persistence of the HBV genome in the hepatocyte’s nucleus generates a stable source of viral RNAs and subsequently proteins which play important roles in immune escape mechanisms and liver disease progression. Therapies aiming at efficiently and durably eliminating viral gene expression are still required. In this study, we identified the nuclear partners of the HBV Core protein (HBc) to understand how this structural protein, responsible for capsid assembly in the cytoplasm, could also regulate viral gene expression. The HBc interactome was found to consist primarily of RNA-binding proteins (RBPs). One of these RBPs, SRSF10, was demonstrated to restrict HBV RNA levels and a drug, able to alter its phosphorylation, behaved as an antiviral compound capable of reducing viral gene expression. Altogether, this study sheds new light novel regulatory functions of HBc and provides information relevant for the development of antiviral strategies aiming at preventing viral gene expression.

Background & Aims HBV persists in the nucleus of infected hepatocytes as a covalently closed circular DNA (cccDNA) episome that constitutes the template for viral RNA and protein synthesis. Both HBx and HBc (core) viral proteins associate with cccDNA but, while HBx is required for viral transcription, the role of HBc is still unclear. The aim of this study was to determine if HBc derived from incoming nucleocapsid can associate with cccDNA before the onset of viral transcription and protein production. Methods Chromatin immunoprecipitation assays were performed in native conditions. In addition, differentiated HepaRG (dHepaRG) cells infected with HBx-deficient HBV were used to investigate if HBc delivered by incoming virions can associate with cccDNA. Results Our results indicate that HBc can associate with cccDNA in the absence of viral transcription and de novo protein synthesis. In dHepaRG cells, this association is stable for at least 6 weeks. Conclusion These results suggest that virion-delivered HBc may participate at an early stage of cccDNA formation and/or transcription. Lay summary The hepatitis B virus genome is released into the nucleoplasm of infected cells after disassembly of the viral nucleocapsids at the nuclear membrane. Herein, we show for the first time that virion-delivered hepatitis B core protein, a component of the viral capsid, can stably associate with integrated viral DNA., Graphical abstract, Highlights • The HBV episome (cccDNA) is formed in the nucleus following disassembly of incoming nucleocapsids. • Native ChIP analysis indicates that virion-delivered HBc proteins can stably associate with cccDNA. • Association of virion-delivered HBc does not require de novo viral protein synthesis. • These results suggest that virion-delivered HBc may participate in cccDNA formation and/or transcriptional regulation.

GAPDH is emerging as a key player in T cell development and function. To investigate the role of GAPDH in T cells, we generated a transgenic mouse model overexpressing GAPDH in the T cell lineage. Aged mice developed a peripheral Tfh-like lymphoma that recapitulated key molecular, pathological, and immunophenotypic features of human angioimmunoblastic T cell lymphoma (AITL). GAPDH induced non-canonical NF-κB pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-κB pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-κB signaling in AITL and provide a model for future AITL therapeutic investigations.

Virgin rapeseed (Brassica napus) oil is a valuable niche product, if delivered with a high quality. In this study, the effects of moist storage of B. napus seeds for 1 to 4 days on the seed metabolome and the chemo-sensory properties of the produced oils were determined. The concentrations of several primary metabolites, including monosaccharides and amino acids, rapidly increased in the seeds, probably indicating the breakdown of storage compounds to support seed germination. Seed concentrations of indole glucosinolates increased with a slight time offset suggesting that amino acids may be used to modify secondary metabolism. The volatile profiles of the oils were pronouncedly influenced by moist seed storage, with the sensory quality of the oils decreasing. This study provides a direct time-resolved link between seed metabolism under moist conditions and the quality of the resulting oils, thereby emphasizing the crucial role of dry seed storage in ensuring high oil quality.