Adaptation of Poa alpina to altitude and land use in the Swiss Alps

Current land use and climate change are prompting questions about the ability of plants to adapt to such environmental change. Therefore, we experimentally addressed plant performance and quantitative-genetic diversity of the common Alpine Meadow Grass Poa alpina. We asked how land use and altitude affect the occurrence of P. alpina in the field and whether its common-garden performance suggests adaptation to conditions at plant origin and differences in quantitative genetic diversity among plant origins. Among 216 candidate grassland sites of different land use and altitude from 12 villages in the Swiss Alps, P. alpina occurred preferentially in fertilized and grazed sites and at higher elevations. In a common garden at 1,500m asl, we grew two plants of >600 genotypes representing 78 grassland sites. After 2years, nearly 90% of all plants had reproduced. In agreement with adaptive advantages of vegetative reproduction at higher altitudes, only 23% of reproductive plants from lower altitudes reproduced via vegetative bulbils, but 55% of plants from higher altitudes. In agreement with adaptive advantages of reproduction in grazed sites, allocation to reproductive biomass was higher in plants from grazed grasslands than from mown ones. For 53 grasslands, we also investigated broad-sense heritability H2, which was significant for all studied traits and twice as high for grazed as for mown grasslands. Moreover, possibly associated with their higher landscape diversity, H2 was higher for sites of villages of Romanic cultural tradition than for those of Germanic and Walser traditions. We suggest promoting diverse land use regimes to conserve not only landscape and plant species diversity, but also adaptive genetic differentiation and heritable genetic variatio

Microsatellite Diversity of the Agriculturally Important Alpine Grass Poa alpina in Relation to Land Use and Natural Environment

Background and Aims The Alpine Meadow Grass Poa alpina is common in subalpine and alpine natural sites and agriculturally used land, where it is an important fodder grass. Natural factors and human land use are supposed to have been shaping its genetic diversity for hundreds of years. The species comprises sexually and vegetatively reproducing plants. The aim of this study was to investigate the effects of agricultural land use, environmental factors and the mode of reproduction on the distribution of its microsatellite diversity within and among populations and to analyse whether its genetic diversity is correlated with plant species diversity in grassland parcels. Methods Genetic diversity of P. alpina was assessed with five microsatellite markers for 569 plants originating from 20 natural sites and from 54 grassland parcels of different cultural tradition, land use and altitude in the Swiss Alps. Due to polyploidy and frequent aneuploidy of the species, data analyses were based on the presence of microsatellite bands. Key Results A low but significant differentiation was found in microsatellite bands among natural sites and agriculturally used parcels, while their microsatellite band diversity within populations did not differ. An increased differentiation was found in microsatellite bands with increasing geographic distance among parcels, and a differentiation among grazed and mown parcels, and among sexually and vegetatively reproducing populations. Band richness of sampled plants per village was higher for villages where parcels represented more different land-use types. Within populations, microsatellite band diversity was higher in grazed than in mown parcels. Conclusions The diversity of human land use in the Alps was associated with genetic diversity of P. alpina. Therefore, the ongoing socio-economically motivated land-use changes, which reduce the number of different land-use types, will affect the genetic diversity of P. alpina negativel

Omnipresence of leaf herbivory by invertebrates and leaf infection by fungal pathogens in agriculturally used grasslands of the Swiss Alps, but low plant damage

Agriculturally used grasslands in the Alps are characterised by a trade-off between high fodder production in some and high plant species richness in others. In contrast to plant species richness and production, however, little is known on the relevance of biological interactions between plants, invertebrate herbivores, and fungal pathogens for grasslands in the Alps. At the time when the vegetation was fully developed, but prior to agricultural use, we examined whether leaf damage by herbivory and fungal pathogen infection, and their diversity, are affected by plant functional group, land use, and altitude. Moreover, we studied whether extent and diversity of leaf damage are related to each other, to plant species richness, and to standing crop. We recorded the leaf area damaged by ten types of herbivory and five types of fungal pathogen infection on 12,054 plant leaves of legumes, other forbs, and graminoids collected in 215 grassland parcels in 12 valleys in the Swiss Alps. With 83% of all leaves infested, herbivory and fungal pathogen infection were omnipresent. However, only 2.7% leaf area was damaged by herbivory and 1.2% by fungal pathogens. Damage by herbivory was highest on legumes, and damage by fungal pathogens was highest on graminoids. More leaf damage by herbivory occurred in traditionally mown sites and at lower altitudes, while damage by fungal pathogen infection was independent of land use and altitude. Most types of herbivory were found on legumes and on leaves from fertilised sites, whereas the number of fungal pathogen types was highest on graminoids and in unfertilised sites. Larger standing crop was associated with higher leaf damage and diversity of herbivory types per leaf. Neither damage by herbivory nor by fungal pathogens was correlated with plant species diversity. In more plant species rich parcels, the number of herbivory types was lower at the leaf level, but tended to be higher at the parcel level. Our results highlight the omnipresence of plant-herbivore and plant-pathogen interactions. They suggest that current land use changes from mowing to grazing or to abandonment decrease the diversity of herbivory, and that fertilisation decreases pathogen diversity. As our results did not reveal conservation conflicts between diversities of plants, herbivores, and fungal pathogens, and as the damage from herbivory and pathogens is generally low, we conclude that for protecting the high diversity of plant-herbivore and plant-pathogen interactions a diverse low-intensity land use should be maintaine

The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation

Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated.Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually.We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails

Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis

ObjectiveTo identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets.MethodsUsing human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < −2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA.ResultsMost of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media.ConclusionThis study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies

Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming

Rationale Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. Objectives To investigate the role of IL-3 during viral pneumonia in sepsis. Methods We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). Measurements and main results Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. Conclusion Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs

Lack of Chemokine Signaling through CXCR5 Causes Increased Mortality, Ventricular Dilatation and Deranged Matrix during Cardiac Pressure Overload

RATIONALE: Inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), but a role for chemokines is largely unknown. Based on their role in inflammation and matrix remodeling in other tissues, we hypothesized that CXCL13 and CXCR5 could be involved in cardiac remodeling during HF. OBJECTIVE: We sought to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF. METHODS AND RESULTS: Mice harboring a systemic knockout of the CXCR5 (CXCR5(-/-)) displayed increased mortality during a follow-up of 80 days after aortic banding (AB). Following three weeks of AB, CXCR5(-/-) developed significant left ventricular (LV) dilatation compared to wild type (WT) mice. Microarray analysis revealed altered expression of several small leucine-rich proteoglycans (SLRPs) that bind to collagen and modulate fibril assembly. Protein levels of fibromodulin, decorin and lumican (all SLRPs) were significantly reduced in AB CXCR5(-/-) compared to AB WT mice. Electron microscopy revealed loosely packed extracellular matrix with individual collagen fibers and small networks of proteoglycans in AB CXCR5(-/-) mice. Addition of CXCL13 to cultured cardiac fibroblasts enhanced the expression of SLRPs. In patients with HF, we observed increased myocardial levels of CXCR5 and SLRPs, which was reversed following LV assist device treatment. CONCLUSIONS: Lack of CXCR5 leads to LV dilatation and increased mortality during pressure overload, possibly via lack of an increase in SLRPs. This study demonstrates a critical role of the chemokine CXCL13 and CXCR5 in survival and maintaining of cardiac structure upon pressure overload, by regulating proteoglycans essential for correct collagen assembly

Drivers of grassland biodiversity in the Swiss Alps

Die einzigartige Kulturlandschaft der Alpen mit ihrem vielfältigen Mosaik aus Wiesen und Weiden ist im Laufe von Jahrhunderten durch menschliche Nutzung entstanden. Besonders Grasland leistet einen wichtigen Beitrag zur hohen biologischen Vielfalt (Biodiversität) in den Alpen. Sozioökonomische Veränderungen in der Landwirtschaft lassen negative Auswirkungen auf die Biodiversität erwarten. Wir untersuchten auf 216 landwirtschaftlichen Parzellen unterschiedlicher Nutzung und Höhenlage in 12 Gemeinden der drei kulturellen Traditionen Romanisch, Germanisch/Alemannisch und Walser die Einflüsse von kulturellen Traditionen, Höhe und Landnutzung auf verschiedene Ebenen der Biodiversität (Vielfalt der Landnutzungstypen, Pflanzenarten, biologische Interaktionen, Gene). Wir stellten fest, dass in den Alpen die Biodiversität ein Produkt Jahrhunderte langer menschlicher Einflüsse ist. Verschiedene Ebenen der Biodiversität werden von unterschiedlichen Faktoren verschieden beeinflusst. Zunehmende Monotonisierung in der Landwirtschaft sowie Abwanderung aus Regionen wird die Biodiversität drastisch reduzieren, gleichzeitig die Anziehungskraft für Touristen mindern und die Überreste des Kulturerbes in den Schweizer Alpen gefährden. Wir schlussfolgern, dass eine möglichst vielfältige Landnutzung die Biodiversität auf allen Ebenen am besten fördert. Zur Umsetzung ist allerdings erweiterte finanzielle Unterstützung nicht nur für einzelne Landwirte, sondern auch auf regionaler Ebene notwendig, um die vielfältige Landschaft der Alpen und ihre hohe Biodiversität zu schützen. The unique cultural landscape of the Alps and its diverse mosaic of meadows and pastures have developed over hundreds of years of human land use. Particularly grassland contributes to the high biodiversity of the Alps. Socio-economic changes in land use in particular in mountain areas negatively affect biodiversity. In 12 municipalities, four of each of the three cultural traditions Romanic, Germanic/ Alemannic, and Walser, we selected 216 grassland parcels of different land use and altitude. We studied the effects of cultural traditions, altitude, and land use on the different levels of biodiversity comprehensively (diversity of land use types, diversity of plant species, diversity of biological interactions, genetic diversity). We found that in the Alps, biodiversity on all levels is a product of hundreds of years of human land use. Different levels of biodiversity are driven by different factors. Increasingly monotonic agricultural land use or even abandonment of whole regions will drastically reduce biodiversity, and at the same time, it will reduce landscape attractiveness for tourists and endanger the remnants of cultural heritage in the Swiss Alps. We conclude that ideally a high diversity of land use types promotes a high biodiversity on all levels. Therefore, further financial incentives are necessary not only for single farmers, but also on regional scale to conserve the diverse landscapes of the Alps and its biodiversity on all levels