The worldwide retreat of glaciers is causing a faster than ever increase in ice‐free areas that are leading to the emergence of new ecosystems. Understanding the dynamics of these environments is ...critical to predicting the consequences of climate change on mountains and at high latitudes. Climatic differences between regions of the world could modulate the emergence of biodiversity and functionality after glacier retreat, yet global tests of this hypothesis are lacking. Nematodes are the most abundant soil animals, with keystone roles in ecosystem functioning, but the lack of global‐scale studies limits our understanding of how the taxonomic and functional diversity of nematodes changes during the colonization of proglacial landscapes. We used environmental DNA metabarcoding to characterize nematode communities of 48 glacier forelands from five continents. We assessed how different facets of biodiversity change with the age of deglaciated terrains and tested the hypothesis that colonization patterns are different across forelands with different climatic conditions. Nematodes colonized ice‐free areas almost immediately. Both taxonomic and functional richness quickly increased over time, but the increase in nematode diversity was modulated by climate, so that colonization started earlier in forelands with mild summer temperatures. Colder forelands initially hosted poor communities, but the colonization rate then accelerated, eventually leveling biodiversity differences between climatic regimes in the long term. Immediately after glacier retreat, communities were dominated by colonizer taxa with short generation time and r‐ecological strategy but community composition shifted through time, with increased frequency of more persister taxa with K‐ecological strategy. These changes mostly occurred through the addition of new traits instead of their replacement during succession. The effects of local climate on nematode colonization led to heterogeneous but predictable patterns around the world that likely affect soil communities and overall ecosystem development.
The worldwide retreat of glaciers is expanding ice‐free areas, creating new ecosystems. Our global‐scale study reveals that deglaciation is followed by heterogeneous but predictable soil colonization dynamics by nematodes, depending on local climates. Cold forelands initially hosted limited biodiversity, but here the colonization rate was higher, so that in the long term (after ~150 years) biodiversity equalized that of mild climates, where the colonization started earlier. Nematode communities experienced functional changes involving a shift from communities dominated by fast‐reproducing taxa (r‐ecological strategy) to an increased frequency of more persister taxa (K‐strategy) during colonization.
The mechanisms underlying plant succession remain highly debated. Due to the local scope of most studies, we lack a global quantification of the relative importance of species addition 'versus' ...replacement. We assessed the role of these processes in the variation (β-diversity) of plant communities colonizing the forelands of 46 retreating glaciers worldwide, using both environmental DNA and traditional surveys. Our findings indicate that addition and replacement concur in determining community changes in deglaciated sites, but their relative importance varied over time. Taxa addition dominated immediately after glacier retreat, as expected in harsh environments, while replacement became more important for late-successional communities. These changes were aligned with total β-diversity changes, which were more pronounced between early-successional communities than between late-successional communities (>50 yr since glacier retreat). Despite the complexity of community assembly during plant succession, the observed global pattern suggests a generalized shift from the dominance of facilitation and/or stochastic processes in early-successional communities to a predominance of competition later on.
Glacier forefields have long provided ecologists with a model to study patterns of plant succession following glacier retreat. While plant-survey-based approaches applied along chronosequences ...provide invaluable information on plant communities, the “space-for-time” approach assumes environmental uniformity and equal ecological potential across sites and does not account for spatial variability in initial site conditions. Remote sensing provides a promising avenue for assessing plant colonization dynamics using a so-called “real-time” approach. Here, we combined 36 years of Landsat imagery with extensive field sampling along chronosequences of deglaciation for eight glacier forefields in the southwestern European Alps to investigate the heterogeneity of early plant succession dynamics. Based on the two complementary and independent approaches, we found strong variability in the time lag between deglaciation and colonization by plants and in subsequent growth rates and in the composition of early plant succession. All three parameters were highly dependent on the local environmental context, i.e., neighboring vegetation cover and energy availability linked to temperature and snowmelt gradients. Potential geomorphological disturbance did not emerge as a strong predictor of succession parameters, which is perhaps due to insufficient spatial resolution of predictor variables. Notably, the identity of pioneer plant species was highly variable, and initial plant community composition had a much stronger influence on plant assemblages than elapsed time since deglaciation. Overall, both approaches converged towards the conclusion that early plant succession is not stochastic as previous authors have suggested but rather determined by local ecological context. We discuss the importance of scale in deciphering the complexity of plant succession in glacier forefields and provide recommendations for improving botanical field surveys and using Landsat time series in glacier forefield systems. Our work demonstrates complementarity between remote sensing and field-based approaches for both understanding and predicting future patterns of plant succession in glacier forefields.
El acelerado retroceso glaciar debido al actual calentamiento global conlleva nuevos desafíos para las comunidades vegetales altoandinas, especialmente durante el establecimiento de nuevos bofedales. ...Existe una confusión de ritmo entre el tiempo necesario para la colonización vegetal y el tiempo requerido para desarrollarse en ese tipo de ambiente, posterior al retroceso glaciar (específicamente la formación de suelos). Como resultado, hacemos la hipótesis que las nuevas comunidades sean diferentes de las existentes y empobrecidos en especies estrictamente altoandinas. Este artículo propone y discute metodologías de investigación para examinar las modalidades de formación de nuevas comunidades vegetales altoandinas, posterior al acelerado retroceso glaciar en los Andes tropicales. Se utilizan cuatro cronosecuencias post-glaciales recientes (cada una entre 0 y 38 años después del retroceso glaciar) para estudiar los primeros pasos de sucesión primaria bajo los efectos del calentamiento global. Para evaluar la vegetación se propone utilizar cuadrantes de 1 m² y realizar por lo menos 15 repeticiones en cada banda de desglaciación (cuatro bandas en cada cronosecuencia). Discutimos mediciones bióticas y abióticas que permiten examinar los efectos 1) de los límites de dispersión de cada especie, 2) del estrés abiótico (temperatura, humedad, viento) a lo largo del retroceso glaciar y 3) de la presencia/ausencia de organismos nodrizas como plantas y costra biológica, sobre la sucesión primaria. La comprobación de estos métodos en campo nos permitió discutir la pertinencia de cada una y de proponer métodos complementarios para estudios futuros en la misma temática.
Glaciers in the Tropical Andes and other mountain regions are retreating widely. The emerging glacier forelands, often associated with physical risks and hazards, are not only the stage for many ...processes and paraglacial dynamics that shape the landscapes following glacier retreat. At the same time as glacier retreat, soils develop, and the new landscape is quickly colonized by plants, animals, and the other phyla (i.e., primary succession). This contribution focuses on the novel proglacial ecosystems resulting from accelerated biophysical processes and altered community assembly. Through a compilation of soil and plant chronosequence studies, we present the main characteristics of proglacial pedogenesis and vegetation succession in areas of the Cordillera Blanca deglacierized since the Little Ice Age. We highlight the presence of peatlands after approximately 150 years of deglacierization. In the Cordillera Blanca, the implications for current and future proglacial landscape management and cascading ecological and societal consequences are numerous. Proglacial landscapes can act as hydrological buffers and filters, store carbon, and function as refuges for cold-adapted species, thus favoring high Andean biodiversity conservation.
Recent studies demonstrated that autophagy is an important regulator of innate immune response. However, the mechanism by which autophagy regulates natural killer (NK) cell-mediated antitumor immune ...responses remains elusive. Here, we demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. Inhibition of autophagy by targeting beclin1 (BECN1) restored granzyme B levels in hypoxic cells in vitro and induced tumor regression in vivo by facilitating NK-mediated tumor cell killing. Together, our data highlight autophagy as a mechanism underlying the resistance of hypoxic tumor cells to NK-mediated lysis. The work presented here provides a cutting-edge advance in our understanding of the mechanism by which hypoxia-induced autophagy impairs NK-mediated lysis in vitro and paves the way for the formulation of more effective NK cell-based antitumor therapies.
April 15th, 2019: Notre-Dame Cathedral in Paris was burning, the spire collapsed on the nave, vaults crumbled and most of the timber roof was gone. In the post-disaster context, the authenticity and ...the monitoring of the archaeological remains are crucial for their potential reuse during reconstruction. This paper analyzes the collapsed transverse arch from the nave of Notre-Dame as a case study of reconstruction, using the digital twin framework. We propose four facets for the digital twin experiment-physical anastylosis, reverse engineering, spatio-temporal tracking of assets, and operational research-that are described in detail, while being assembled to support a hybrid reconstruction hypothesis. The digital twin can realize the parallel unfolding of physical-native and digital-native processes, while acquiring and storing heterogeneous information as semantically structured data. The results demonstrate that the proposed modeling method facilitates the formalization and validation of the reconstruction problem and increases solutions performances. As result, we present a digital twin framework application ranging from acquisition to data processing that informs a successful hybrid reconstruction hypothesis.
Background
Numerous patient‐based studies have highlighted the protective role of immunoglobulin E‐mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the ...mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection.
Methods
An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1‐KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA‐sequencing. Peripheral as well as tumor‐associated immune cells were characterized by flow cytometry. The impact of allergy‐related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets.
Results
We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro‐inflammatory‐like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T‐cells in the circulation as well as tumor‐infiltrating CD4+T‐cells. The survival benefit conferred by AAI was lost in mice devoid of adaptive immunity.
Conclusion
Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy‐induced immune protection against GBM.
Allergy‐induced protection against GBM is recapitulated in a preclinical syngeneic mouse model. Allergic airway inflammation skews microglia toward pro‐inflammatory and antigen‐presenting like‐states, uncovering a gene‐signature in mice associated with improved patient survival and reduced local immunosuppression in glioma patients. Allergic airway inflammation promotes the recruitment of CD4+T‐cells within the tumor microenvironment and mitigates glioma‐induced systemic immunosuppression.Abbreviations: AAI, allergic airway inflammation; GBM, glioblastoma; Neu, neutrophil; TME, tumor‐microenvironment.
Background. Despite the introduction of an effective serogroup A conjugate vaccine (MenAfriVac™), sporadic epidemics of other Neisseria meningitidis serogroups remain a concern in Africa. Polyvalent ...meningococcal conjugate (PMC) vaccines may offer alternatives to current strategies that rely on routine infant vaccination with MenAfriVac plus, in the event of an epidemic, district-specific reactive campaigns using polyvalent meningococcal polysaccharide (PMP) vaccines. Methods. We developed an agent-based transmission model of N. meningitidis in Niger to compare the health effects and costs of current vaccination practice and 3 alternatives. Each alternative replaces MenAfriVac in the infant vaccination series with PMC and either replaces PMP with PMC for reactive campaigns or implements a one-time catch up campaign with PMC for children and young adults. Results. Over a 28-year period, replacement of MenAfriVac with PMC in the infant immunization series and of PMP in reactive campaigns would avert 63% of expected cases (95% prediction interval 49%–75%) if elimination of serogroup A is not followed by serogroup replacement. At a PMC price of $4/dose, this would cost $1412 ($81–$3510) per disability-adjusted life-year (DALY) averted. If serogroup replacement occurs, the cost-effectiveness of this strategy improves to $662 (cost-saving, $2473) per DALY averted. Sensitivity analyses accounting for incomplete laboratory confirmation suggest that a catch-up PMC campaign would also meet standard cost-effectiveness thresholds. Limitations. The assumption that polyvalent vaccines offer similar protection against all serogroups is simplifying. Conclusions. The use of PMC vaccines to replace MenAfriVac in routine infant immunization and in district-specific reactive campaigns would have important health benefits and is likely to be cost-effective in Niger. An additional PMC catch-up campaign would also be cost-effective if we account for incomplete laboratory reporting.
Abstract
Natural killer (NK) cells are effectors of the innate immune system, able to kill cancer cells through the release of the cytotoxic protease granzyme B. NK-based therapies have recently ...emerged as promising anticancer strategies. However, it is well established that hypoxic tumor microenvironment interferes with the antitumor function of immune cells and constitutes a major obstacle for defining cancer immunotherapies. Recent studies demonstrated that autophagy regulates the innate immune response by mechanisms which are not fully understood. In this study, we showed that hypoxia decreases breast cancer cell susceptibility to NK-mediated lysis by a mechanism involving the activation of autophagy in tumor cells. Targeting autophagy was sufficient to restore NK-mediated tumor cell killing. We showed that the resistance of hypoxic tumor cells was neither related to a defect in their recognition by NK cells, nor to a defect in the cytolytic function of NK cells toward hypoxic cells. We provided evidence that autophagy activation degrades NK-derived granzyme B in lysosomes of hypoxic cells making them less sensitive to NK-mediated killing. Genetic and pharmacological inhibition of autophagy restored granzyme B levels and reverted the resistance of hypoxic cells in vitro. Our results highlight autophagy as a critical factor in modulating NK-mediated anti-tumor immune response. We have validated this concept in vivo by showing that targeting autophagy significantly improved NK-mediated tumor shrinking in breast and melanoma models. This study provides a cutting-edge advance in our understanding of how hypoxia-induced autophagy impairs NK-mediated lysis and paves the way for formulating more effective NK-based antitumor therapy by combining autophagy inhibitors.
Citation Format: Joanna Baginska, Elodie Viry, Guy Berchem, Aurélie Poli, Muhammad Zaeem Noman, Kris van Moer, Sandrine Medves, Takouhie Mgrditchian, Jacques Zimmer, Anais Oudin, Simone P. Niclou, R. Chris Bleackley, Salem Chouaib, Bassam Janji. Autophagic degradation of granzyme B impairs NK-mediated killing of hypoxic tumor cells. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 156. doi:10.1158/1538-7445.AM2014-156
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