cytoNet: Spatiotemporal network analysis of cell communities

We introduce cytoNet, a cloud-based tool to characterize cell populations from microscopy images. cytoNet quantifies spatial topology and functional relationships in cell communities using principles of network science. Capturing multicellular dynamics through graph features, cytoNet also evaluates the effect of cell-cell interactions on individual cell phenotypes. We demonstrate cytoNet’s capabilities in four case studies: 1) characterizing the temporal dynamics of neural progenitor cell communities during neural differentiation, 2) identifying communities of pain-sensing neurons in vivo, 3) capturing the effect of cell community on endothelial cell morphology, and 4) investigating the effect of laminin α4 on perivascular niches in adipose tissue. The analytical framework introduced here can be used to study the dynamics of complex cell communities in a quantitative manner, leading to a deeper understanding of environmental effects on cellular behavior. The versatile, cloud-based format of cytoNet makes the image analysis framework accessible to researchers across domains.     

Structural Correlates of Antibodies Associated with Acute Reversal of Amyloid ��-related Behavioral Deficits in a Mouse Model of Alzheimer Disease

Immunotherapy targeting of amyloid β (Aβ) peptide in transgenic mouse models of Alzheimer disease (AD) has been widely demonstrated to resolve amyloid deposition as well as associated neuronal, glial, and inflammatory pathologies. These successes have provided the basis for ongoing clinical trials of immunotherapy for treatment of AD in humans. Acute as well as chronic Aβ-targeted immunotherapy has also been demonstrated to reverse Aβ-related behavioral deficits assessing memory in AD transgenic mouse models. We observe that three antibodies targeting the same linear epitope of Aβ, Aβ_3–7, differ in their ability to reverse contextual fear deficits in Tg2576 mice in an acute testing paradigm. Reversal of contextual fear deficit by the antibodies does not correlate with in vitro recognition of Aβ in a consistent or correlative manner. To better define differences in antigen recognition at the atomic level, we determined crystal structures of Fab fragments in complex with Aβ. The conformation of the Aβ peptide recognized by all three antibodies was highly related and is also remarkably similar to that observed in independently reported Aβ:antibody crystal structures. Sequence and structural differences between the antibodies, particularly in CDR3 of the heavy chain variable region, are proposed to account for differing in vivo properties of the antibodies under study. These findings provide a structural basis for immunotherapeutic strategies targeting Aβ species postulated to underlie cognitive deficits in AD.     

Multiple models and experiments underscore large uncertainty in soil carbon dynamics

Soils contain more carbon than plants or the atmosphere, and sensitivities of soil organic carbon (SOC) stocks to changing climate and plant productivity are a major uncertainty in global carbon cycle projections. Despite a consensus that microbial degradation and mineral stabilization processes control SOC cycling, no systematic synthesis of long-term warming and litter addition experiments has been used to test process-based microbe-mineral SOC models. We explored SOC responses to warming and increased carbon inputs using a synthesis of 147 field manipulation experiments and five SOC models with different representations of microbial and mineral processes. Model projections diverged but encompassed a similar range of variability as the experimental results. Experimental measurements were insufficient to eliminate or validate individual model outcomes. While all models projected that CO₂ efflux would increase and SOC stocks would decline under warming, nearly one-third of experiments observed decreases in CO₂ flux and nearly half of experiments observed increases in SOC stocks under warming. Long-term measurements of C inputs to soil and their changes under warming are needed to reconcile modeled and observed patterns. Measurements separating the responses of mineral-protected and unprotected SOC fractions in manipulation experiments are needed to address key uncertainties in microbial degradation and mineral stabilization mechanisms. Integrating models with experimental design will allow targeting of these uncertainties and help to reconcile divergence among models to produce more confident projections of SOC responses to global changes.     

The paleoanthropology of Greece

European paleoanthropology and paleolithic archeology were already well‐established by the early twentieth century. The human fossil record from this continent is the longest known and perhaps most intensively studied. Nonetheless, important gaps remain to this day in the map of Pleistocene Europe; perhaps the most glaring of these is located in the southeastern corner of the continent. This region's record is critical for addressing questions about the course of human evolution in Europe because its geographic position lends it a dual role: on one hand, it encompasses a frequently hypothesized dispersal corridor from Africa into Europe for both archaic and early modern humans; on the other, as one of the three Mediterranean peninsulas, it acted as a refugium for plant, animal, and, most likely, human populations during glacial conditions. This article is a review of the paleoanthopological record of Greece, one of the least known in Europe.     

Tracking nutrients in space and time: Interactions between grazing lawns and drought drive abundances of tallgrass prairie grasshoppers

1. We contrast the response of arthropod abundance and composition to bison grazing lawns during a drought and non‐drought year, with an emphasis on acridid grasshoppers, an important grassland herbivore.
2. Grazing lawns are grassland areas where regular grazing by mammalian herbivores creates patches of short‐statured, high nutrient vegetation. Grazing lawns are predictable microsites that modify microclimate, plant structure, community composition, and nutrient availability, with likely repercussions for arthropod communities.
3. One year of our study occurred during an extreme drought. Drought mimics some of the effects of mammalian grazers: decreasing above‐ground plant biomass while increasing plant foliar percentage nitrogen.
4. We sampled arthropods and nutrient availability on and nearby (“off”) 10 bison‐grazed grazing lawns in a tallgrass prairie in NE Kansas. Total grasshopper abundance was higher on grazing lawns and the magnitude of this difference increased in the wetter year of 2019 compared to 2018, when drought led to high grass foliar nitrogen concentrations on and off grazing lawns. Mixed‐feeding grasshopper abundances were consistently higher on grazing lawns while grass‐feeder and forb‐feeder abundances were higher on lawns only in 2019, the wetter year. In contrast, the abundance of other arthropods (e.g., Hemiptera, Hymenoptera, and Araneae) did not differ on and off lawns, but increased overall in 2019, relative to the drought of 2018.
5. Understanding these local scale patterns of abundances and community composition improves predictability of arthropod responses to ongoing habitat change.