Multiple roles for UV RESISTANCE LOCUS8 in regulating gene expression and metabolite accumulation in arabidopsis under solar ultraviolet radiation

Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV

Modelos de endemicidad a lo largo de un gradiente altitudinal en Sierra Nevada (España) y Lefka Ori (Creta, Grecia)

Aim: High mountains in the Mediterranean region of Europe are particularly rich in endemic vascular plants. We aimed to compare the altitudinal patterns of vascular plant species richness and the proportion of endemic species in two Mediterranean region: Lefka Ori on the island of Crete (Greece) and Sierra Nevada on the Iberian peninsula. Location: Sierra Nevada, Granada (Spain); Lefka Ori, Crete (Greece). Methods: Data from standardised permanent plots settings on summit sites (comprising eight plot sectors, covering the upeermost 10 altitudinal metres) of different elevations were used (GLORIA Multi-Summit approach; www.gloria.ac.at). Species numbers, rates of endemic species, and soils temperature were compared by means of ANCOVA and linear regression. Results: The two regions, though climatically similar, showed strikingly different patterns: In Sierra Nevada, the proportion of endemic vascular plants (species restricted to Sierra Nevada) showed a stepwise increase from the lowest to the highest summit. In contrast, the proportion of endemic species restricted to Crete was not significantly different between the four summits in Lefka Ori. In both regions the observed trends were largely consistent with the altitudinal distribution of the endemic species obtained from standard floras. Main conclusions: The geographic positions of the two regions, i.e. island versus mainland and the higher elevation of Sierra Nevada are suggested to be the primary causes of the observed differences. The high degree of endemism in the cold environments of Mediterranean mountains’ upper bioclimatic zones indicates a pronounced vulnerability to the impacts of climate change. A continued and intensified species monitoring in the mountains around the Mediterranean basin, therefore, should be considered as a priority research task.Objetivo: Las zonas de alta montaña en la región mediterránea europea son particularmente ricas en plantas vasculares endémicas. Nuestro objetivo es comparar los modelos altitudinales para la riqueza de plantas vasculares y la proporción de endemismos en dos regiones mediterráneas: Lefka Ori en la isla de Creta (Grecia) y Sierra Nevada en la Península Ibérica. Localización: Sierra Nevada, Granada (España); Lefka Ori, Creta (Grecia). Método: Los datos proceden de un muestreo estandarizado en varias cimas situadas a diferentes altitudes (GLORIA Multi-Summit approach; www.gloria.ac.at). El número de especies, tasas de endemicidad, y temperatura del suelo se compararon por medio de ANCOVA y regresión lineal. Resultados: Las dos regiones objeto de análisis, aunque similares climáticamente, muestran patrones llamativamente diferentes: en Sierra Nevada, la proporción de plantas vasculares endémicas (especies restringidas a Sierra Nevada) muestra un incremento gradual desde la cima más baja a la más alta. En contraste, la proporción de endemismos restringidos a Creta no fue significativamente diferente entre las cuatro cimas de Lefka Ori. Las tendencias observadas en ambas regiones fueron en gran parte consistentes con la distribución de las especies endémicas obtenida de las floras para cada región. Conclusiones principales: La posición geográfica de ambas regiones, por ejemplo. isla frente a continente, y la mayor elevación de Sierra Nevada se sugieren como las principales causas de las diferencias observadas. El alto grado de endemicidad en los ambientes fríos de las zonas bioclimáticas superiores de las montañas mediterráneas evidencia una marcada vulnerabilidad a los impactos del cambio climático. Por lo tanto, el seguimiento continuado e intensivo de las especies de montaña alrededor de la cuenca mediterránea, debería considerarse como una tarea investigadora prioritaria.He set up of the permanent plots and data collection was supported by the FP-5 project GLORIA-Europe (2001-2003) No EVK2-2000-00056 of the European Commission

Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis

Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis

Dispersion strengthening in vanadium microalloyed steels processed by simulated thin slab casting and direct charging. Part 2 - chemical characterisation of dispersion strengthening precipitates

The composition of the sub-15 nm particles in six related vanadium high strength low alloy steels, made by simulated thin slab direct charged casting, has been determined using electron energy loss spectroscopy (EELS). Such particles are considered to be responsible for dispersion hardening. For the first time, particles down to 4 nm in size have had their composition fully determined. In all the steels, the particles were nitrogen and vanadium rich and possibly slightly sub-stoichiometric carbonitrides. Equilibrium thermodynamics predicted much higher carbon to metal atomic ratios than observed in all cases so that kinetics and mechanical deformation clearly control the precipitation process. Thus it is important to formulate the steel with this in mind

Loss of secreted gelsolin enhances response to anticancer therapies

Type 1 conventional dendritic cells (cDC1) play a critical role in priming anticancer cytotoxic CD8+ T cells. DNGR-1 (a.k.a. CLEC9A) is a cDC1 receptor that binds to F-actin exposed on necrotic cancer and normal cells. DNGR-1 signaling enhances cross-presentation of dead-cell associated antigens, including tumor antigens. We have recently shown that secreted gelsolin (sGSN), a plasma protein, competes with DNGR-1 for binding to dead cell-exposed F-actin and dampens anticancer immunity. Here, we investigated the effects of loss of sGSN on various anticancer therapies that are thought to induce cell death and provoke an immune response to cancer. We compared WT (wildtype) with Rag1-/- , Batf3-/- , Clec9agfp/gfp , sGsn-/- or sGsn-/- Clec9agfp/gfp mice implanted with transplantable tumor cell lines, including MCA-205 fibrosarcoma, 5555 BrafV600E melanoma and B16-F10 LifeAct (LA)-ovalbumin (OVA)-mCherry melanoma. Tumor-bearing mice were treated with (1) doxorubicin (intratumoral) chemotherapy for MCA-205, (2) BRAF-inhibitor PLX4720 (oral gavage) targeted therapy for 5555 BrafV600E, and (3) X-ray radiotherapy for B16 LA-OVA-mCherry. We confirmed that efficient tumor control following each therapy requires an immunocompetent host as efficacy was markedly reduced in Rag1-/- compared with WT mice. Notably, across all the therapeutic modalities, loss of sGSN significantly enhanced tumor control compared with treated WT controls. This was an on-target effect as mice deficient in both sGSN and DNGR-1 behaved no differently from WT mice following therapy. In sum, we find that mice deficient in sGsn display enhanced DNGR-1-dependent responsiveness to chemotherapy, targeted therapy and radiotherapy. Our findings are consistent with the notion some cancer therapies induce immunogenic cell death (ICD), which mobilizes anticancer T cells. Our results point to cDC1 and DNGR-1 as decoders of ICD and to sGSN as a negative regulator of such decoding, highlighting sGSN as a possible target in cancer treatment. Further prospective studies are warranted to identify patients who may benefit most from inhibition of sGSN function

TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation, myelopoiesis is modulated to rapidly meet the demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites

τ\tauSPECT: A spin-flip loaded magnetic ultracold neutron trap for a determination of the neutron lifetime

The confinement of ultracold neutrons (UCNs) in a three dimensional magnetic field gradient trap allows for a measurement of the free neutron lifetime with superior control over spurious loss channels and can provide a large kinetic energy acceptance to enhance statistical sensitivity. In this paper, we present the first successful implementation of a pulsed spin-flip based loading scheme for a three-dimensional magnetic UCN trap. The measurements with the $\tau$SPECT experiment were performed at the pulsed UCN source of the research reactor TRIGA Mainz. We report on detailed investigations of major systematic effects influencing the neutron storage time, statistically limited by the size of the recorded data set. The extracted neutron storage time constant of $\tau = 859(16)\mathrm{s}$ is compatible with, but not to be interpreted as, a measurement of the free neutron lifetime.Comment: 15 pages, 19 figure

Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages

Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif

RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells

RUNX1 is a transcription factor that plays key roles in hematopoietic development and in hematopoiesis and lymphopoiesis. In this article, we report that RUNX1 regulates a gene expression program in naive mouse B cells that affects the dynamics of cell cycle entry in response to stimulation of the BCR. Conditional knockout of Runx1 in mouse resting B cells resulted in accelerated entry into S-phase after BCR engagement. Our results indicate that Runx1 regulates the cyclin D2 (Ccnd2) gene, the immediate early genes Fosl2, Atf3, and Egr2, and the Notch pathway gene Rbpj in mouse B cells, reducing the rate at which transcription of these genes increases after BCR stimulation. RUNX1 interacts with the chromatin remodeler SNF-2-related CREB-binding protein activator protein (SRCAP), recruiting it to promoter and enhancer regions of the Ccnd2 gene. BCR-mediated activation triggers switching between binding of RUNX1 and its paralog RUNX3 and between SRCAP and the switch/SNF remodeling complex member BRG1. Binding of BRG1 is increased at the Ccnd2 and Rbpj promoters in the Runx1 knockout cells after BCR stimulation. We also find that RUNX1 exerts positive or negative effects on a number of genes that affect the activation response of mouse resting B cells. These include Cd22 and Bank1, which act as negative regulators of the BCR, and the IFN receptor subunit gene Ifnar1 The hyperresponsiveness of the Runx1 knockout B cells to BCR stimulation and its role in regulating genes that are associated with immune regulation suggest that RUNX1 could be involved in regulating B cell tolerance