Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease.

The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20+ B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool

Quantifizierung der Porenraumdynamik von organischen Substraten mit Hilfe der Mikro-Computertomographie

Böden sind durch ein dynamisches und heterogenes Porensystem charakterisiert. Die Veränderung von Fließpfaden und damit die Zu-gänglichkeit von Oberflächen ist eine Funktion von hydraulischen (Schrumpfen-Quellen) und mechanischen Kräften, die intern (z.?B. Wurzeln, Regenwürmer) oder extern (Auflasten) zu Porenumverteilungen führen. Dahin gehend variieren In-tensitäts- und Kapazitäts-Kenngrößen, die für Transport- und Speichervorgänge im System Boden-Pflanze-Atmosphäre von Bedeutung sind. Die Mikro-Computertomographie (XMCT) ist eine Methode zur nicht-invasiven Untersu-chung von Böden, mit der sich morpholo-gische und topologische Eigenschaften des Porenraumes mit Hilfe quantitativer Bildauswerteverfahren erfassen und mit physikalischen Funktionen in Beziehun-gen setzen lassen. An ungestörten orga-nischen Proben eines Standortes in Schleswig-Holstein (Wacken) wurden mit der XMCT-Methode wassergehaltsab-hängige Veränderungen von Porenräu-men durch Schrumpfung analysiert

Persistence for stochastic difference equations: A mini-review

Understanding under what conditions populations, whether they be plants, animals, or viral particles, persist is an issue of theoretical and practical importance in population biology. Both biotic interactions and environmental fluctuations are key factors that can facilitate or disrupt persistence. One approach to examining the interplay between these deterministic and stochastic forces is the construction and analysis of stochastic difference equations $X_{t+1}=F(X_t,\xi_{t+1})$ where $X_t \in \R^k$ represents the state of the populations and $\xi_1,\xi_2,...$ is a sequence of random variables representing environmental stochasticity. In the analysis of these stochastic models, many theoretical population biologists are interested in whether the models are bounded and persistent. Here, boundedness asserts that asymptotically $X_t$ tends to remain in compact sets. In contrast, persistence requires that $X_t$ tends to be "repelled" by some "extinction set" $S_0\subset \R^k$. Here, results on both of these proprieties are reviewed for single species, multiple species, and structured population models. The results are illustrated with applications to stochastic versions of the Hassell and Ricker single species models, Ricker, Beverton-Holt, lottery models of competition, and lottery models of rock-paper-scissor games. A variety of conjectures and suggestions for future research are presented.Comment: Accepted for publication in the Journal of Difference Equations and Application

Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline : Decline A Randomized Clinical Trial

IMPORTANCE Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline. OBJECTIVE To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group. DESIGN, SETTING, AND PARTICIPANTS This 12-month randomized, double-masked, placebocontrolled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021. INTERVENTIONS One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (O.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention. MAIN OUTCOMES AND MEASURES Primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed. RESULTS A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.Peer reviewe

Linking the community structure of arbuscular mycorrhizal fungi and plants: a story of interdependence?

Arbuscular mycorrhizal fungi (AMF) are crucial to plants and vice versa, but little is known about the factors linking the community structure of the two groups. We investigated the association between AMF and the plant community structure in the nearest neighborhood of Festuca brevipila in a semiarid grassland with steep environmental gradients, using high-throughput sequencing of the Glomeromycotina (former Glomeromycota). We focused on the Passenger, Driver and Habitat hypotheses: (i) plant communities drive AMF (passenger); (ii) AMF communities drive the plants (driver); (iii) the environment shapes both communities causing covariation. The null hypothesis is that the two assemblages are independent and this study offers a spatially explicit novel test of it in the field at multiple, small scales. The AMF community consisted of 71 operational taxonomic units, the plant community of 47 species. Spatial distance and spatial variation in the environment were the main determinants of the AMF community. The structure of the plant community around the focal plant was a poor predictor of AMF communities, also in terms of phylogenetic community structure. Some evidence supports the passenger hypothesis, but the relative roles of the factors structuring the two groups clearly differed, leading to an apparent decoupling of the two assemblages at the relatively small scale of this study. Community phylogenetic structure in AMF suggests an important role of within-assemblage interactions

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair