Global patterns in endemicity and vulnerability of soil fungi

Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms

Global patterns in endemicity and vulnerability of soil fungi

Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Local dynamics and bending mechanics of mesostructured materials

Die vorliegende Arbeit behandelt die Anwendung der Rasterkraftmikroskopie auf die Untersuchung mesostrukturierter Materialien. Mesostrukturierte Materialien setzen sich aus einzelnen mesoskopen Bausteinen zusammen. Diese Untereinheiten bestimmen im Wesentlichen ihr charakteristisches Verhalten auf äußere mechanische oder elektrische Reize, weshalb diesen Materialien eine besondere Rolle in der Natur sowie im täglichen Leben zukommt. Ein genaues Verständnis der Selbstorganisation dieser Materialien und der Wechselwirkung der einzelnen Bausteine untereinander ist daher von essentieller Bedeutung zur Entwicklung neuer Synthesestrategien sowie zur Optimierung ihrer Materialeigenschaften. Die Charakterisierung dieser mesostrukturierten Materialien erfolgt üblicherweise mittels makroskopischer Analysemethoden wie der dielektrischen Breitbandspektroskopie, Thermogravimetrie sowie in Biegungsexperimenten. In dieser Arbeit wird gezeigt, wie sich diese Analysemethoden mit der Rasterkraftmikroskopie verbinden lassen, um mesostrukturierte Materialien zu untersuchen. Die Rasterkraftmikroskopie bietet die Möglichkeit, die Oberfläche eines Materials abzubilden und zusätzlich dazu seine quantitativen Eigenschaften, wie die mechanische Biegefestigkeit oder die dielektrische Relaxation, zu bestimmen. Die Übertragung makroskopischer Analyseverfahren auf den Nano- bzw. Mikrometermaßstab mittels der Rasterkraftmikroskopie erlaubt die Charakterisierung von räumlich sehr begrenzten Proben bzw. von Proben, die nur in einer sehr kleinen Menge (&lt;10 mg) vorliegen. Darüberhinaus umfasst das Auflösungsvermögen eines Rasterkraftmikroskops, welche durch die Größe seines Federbalkens (50 µm) sowie seines Spitzenradius (5 nm) definiert ist, genau den Längenskalenbereich, der einzelne Atome mit der makroskopischen Welt verbindet, nämlich die Mesoskala. In dieser Arbeit werden Polymerfilme, kolloidale Nanofasern sowie Biomineralien ausführlicher untersucht.rnIm ersten Projekt werden mittels Rasterkraftmikroskopie dielektrische Spektren von mischbaren Polymerfilmen aufgenommen und mit ihrer lokalen Oberflächenstruktur korreliert. Im zweiten Projekt wird die Rasterkraftmikroskopie eingesetzt, um Biegeexperimente an kolloidalen Nanofasern durchzuführen und so ihre Brucheigenschaften genauer zu untersuchen. Im letzten Projekt findet diese Methode Anwendung bei der Charakterisierung der Biegeeigenschaften von Biomineralien. Des Weiteren erfolgt eine Analyse der organischen Zusammensetzung dieser Biomineralien. Alle diese Projekte demonstrieren die vielseitige Einsetzbarkeit der Rasterkraftmikroskopie zur Charakterisierung mesostrukturierter Materialien. Die Korrelation ihrer mechanischen und dielektrischen Eigenschaften mit ihrer topographischen Beschaffenheit erlaubt ein tieferes Verständnis der mesoskopischen Materialien und ihres Verhaltens auf die Einwirkung äußerer Stimuli.rnThis thesis explores the applications of scanning probe microsocpy (SPM) in the study of mesostructured materials. Materials composed of mesoscopic building blocks are defined as mesostructured. A main feature of these materials is that their reaction to external stimuli, e.g. electric or mechanical, is controlled by building blocks that assemble in the mesoscopic regime. These materials play a central role in daily life applications and are found in nature. Knowledge of how mesostructured materials self-assemble and their building blocks interact is of fundamental importance in order to tune their properties and develop new synthesis schemes. Mesostructured materials are typically tested with macroscopic experiments, e.g. broadband dielectric spectroscopy (BDS), bending tests and thermal gravimetric analysis (TGA). In this thesis, ways to combine the main features of these testing experiments with SPM have been demonstrated and used to study mesostructured materials. SPM offers a unique way to image the surface and obtain quantitative properties of mesostructured materials, e.g. mechanical stiffness and dielectric relaxation. Expanding macroscopic testing experiments to the micro- and nanoscale with SPM allows the study of samples that are spatially reduced or prepared in small quantities (&lt;10 mg). Furthermore, the dimensions of the SPM tip (5 nm) and cantilever (~50 µm) makes it an essential tool to cover the length scales that separate single atoms with our macroscopic world, i.e. the mesoscopic regime. Materials of interest throughout this work include polymer blends, colloidal nanofbers and biominerals. In a first project, SPM has been used to obtain dielectric spectra of a miscible polymer blend and correlate surface topography with the local spectra. In a second project, SPM has been used in order to perform bending experiments on colloidal nanofibers and study how they fracture. In a last project, SPM is used to study the bending properties and protein content of biominerals. All these projects demonstrate that SPM is a powerful tool for studying mesostructured materials. Quantitative information about mechanical or dielectric properties in correlation with topographical imaging, allows a deeper understanding of mesostructured materials and their reaction to external stimuli

Glass Transition in Crosslinked Nanocomposite Scaffolds of Gelatin/Chitosan/Hydroxyapatite

The development of biopolymeric scaffolds crosslinked with nanoparticles is an emerging field. Gelatin/chitosan scaffolds are gaining interest in medical areas, e.g., bone tissue engineering, given their suitability for nano-hydroxyapatite incorporation. The glass transition temperature is a thermodynamic property of polymer scaffolds that changes with crosslinker or nanofiller concentration. Here, we report the experimental change in glass transition temperature of gelatin/chitosan scaffolds modified by hydroxyapatite nanoparticles and crosslinker concentration. Our results show synergic effects between nanoparticles and crosslinking, which leads to a non-linear behavior of the glass transition temperature. Furthermore, a theoretical model to predict glass transition is proposed. This model can be used as a mathematical tool for the design of future scaffolds used in bone tissue engineering

Squeezing Drops: Force Measurements of the Cassie-to-Wenzel Transition

Superhydrophobic surfaces have long been the center of attention of many researchers due to their unique liquid repellency and self-cleaning properties. However, these unique properties rely on the stability of the so-called Cassie state, which is a metastable state with air-filled microstructures. This state tends to transit to the stable Wenzel state, where the inside of the microstructures eventually wets. For potential industrial applications, it is therefore critical to maintain the Cassie state. We investigate the Cassie-to-Wenzel transition on superhydrophobic micropillar surfaces by squeezing a water drop between the surface and a transparent superhydrophobic force probe. The probe’s transparency allows the use of top-view optics to monitor the area of the drop as it is squeezed against a micropillared surface. The impalement, or Cassie-to-Wenzel transition, is identified as a sharp decrease in force accompanied by an abrupt change in the drop’s contact area. We compare the force measured by the sensor with the capillary pressure force calculated from the observed drop shape and find a good agreement between both quantities. We also study the force and pressure at impalement as a function of the pillar’s slenderness ratio. Finally, we compare the impalement pressure with three literature predictions and find that our experimental values are consistently lower than the theoretical values. We find that a possible cause of this earlier Cassie-to-Wenzel transition may be the coalescence of the squeezed drop with microdroplets that nucleate around the base of the micropillars

Squeezing Drops: Force Measurements of the Cassie-to-Wenzel Transition

Superhydrophobic surfaces have long been the center of attention of many researchers due to their unique liquid repellency and self-cleaning properties. However, these unique properties rely on the stability of the so-called Cassie state, which is a metastable state with air-filled microstructures. This state tends to transit to the stable Wenzel state, where the inside of the microstructures eventually wets. For potential industrial applications, it is therefore critical to maintain the Cassie state. We investigate the Cassie-to-Wenzel transition on superhydrophobic micropillar surfaces by squeezing a water drop between the surface and a transparent superhydrophobic force probe. The probe’s transparency allows the use of top-view optics to monitor the area of the drop as it is squeezed against a micropillared surface. The impalement, or Cassie-to-Wenzel transition, is identified as a sharp decrease in force accompanied by an abrupt change in the drop’s contact area. We compare the force measured by the sensor with the capillary pressure force calculated from the observed drop shape and find a good agreement between both quantities. We also study the force and pressure at impalement as a function of the pillar’s slenderness ratio. Finally, we compare the impalement pressure with three literature predictions and find that our experimental values are consistently lower than the theoretical values. We find that a possible cause of this earlier Cassie-to-Wenzel transition may be the coalescence of the squeezed drop with microdroplets that nucleate around the base of the micropillars