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Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells
Xenogenic transplantation models have been developed to study human hematopoiesis in immunocompromised murine recipients. They still have limitations and therefore it is important to delineate all players within the bone marrow that could account for species-specific differences. Here, we evaluated the proliferative capacity, morphological and physical characteristics of human CD34+ hematopoietic stem and progenitor cells (HSPCs) after co-culture on murine or human bone marrow-derived mesenchymal stromal cells (MSCs). After seven days, human CD34+CD133– HSPCs expanded to similar extents on both feeder layers while cellular subsets comprising primitive CD34+CD133+ and CD133+CD34– phenotypes are reduced fivefold on murine MSCs. The number of migrating HSPCs was also reduced on murine cells suggesting that MSC adhesion influences cellular polarization of HSPC. We used atomic force microscopy-based single-cell force spectroscopy to quantify their adhesive interactions. We found threefold higher detachment forces of human HSPCs from murine MSCs compared to human ones. This difference is related to the N-cadherin expression level on murine MSCs since its knockdown abolished their differential adhesion properties with human HSPCs. Our observations highlight phenotypic, morphological and adhesive differences of human HSPCs when cultured on murine or human MSCs, which raise some caution in data interpretation when xenogenic transplantation models are used.
The ongoing nutrition transition thwarts long-term targets for food security, public health and environmental protection
The nutrition transition transforms food systems globally and shapes public health and environmental change. Here we provide a global forward-looking assessment of a continued nutrition transition and its interlinked symptoms in respect to food consumption. These symptoms range from underweight and unbalanced diets to obesity, food waste and environmental pressure. We find that by 2050, 45% (39–52%) of the world population will be overweight and 16% (13–20%) obese, compared to 29% and 9% in 2010 respectively. The prevalence of underweight approximately halves but absolute numbers stagnate at 0.4–0.7 billion. Aligned, dietary composition shifts towards animal-source foods and empty calories, while the consumption of vegetables, fruits and nuts increases insufficiently. Population growth, ageing, increasing body mass and more wasteful consumption patterns are jointly pushing global food demand from 30 to 45 (43–47) Exajoules. Our comprehensive open dataset and model provides the interfaces necessary for integrated studies of global health, food systems, and environmental change. Achieving zero hunger, healthy diets, and a food demand compatible with environmental boundaries necessitates a coordinated redirection of the nutrition transition. Reducing household waste, animal-source foods, and overweight could synergistically address multiple symptoms at once, while eliminating underweight would not substantially increase food demand.
A network-based microfoundation of Granovetter’s threshold model for social tipping
Social tipping, where minorities trigger larger populations to engage in collective action, has been suggested as one key aspect in addressing contemporary global challenges. Here, we refine Granovetter’s widely acknowledged theoretical threshold model of collective behavior as a numerical modelling tool for understanding social tipping processes and resolve issues that so far have hindered such applications. Based on real-world observations and social movement theory, we group the population into certain or potential actors, such that – in contrast to its original formulation – the model predicts non-trivial final shares of acting individuals. Then, we use a network cascade model to explain and analytically derive that previously hypothesized broad threshold distributions emerge if individuals become active via social interaction. Thus, through intuitive parameters and low dimensionality our refined model is adaptable to explain the likelihood of engaging in collective behavior where social-tipping-like processes emerge as saddle-node bifurcations and hysteresis. © 2020, The Author(s).
Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform
Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.
Farmer typology to understand differentiated climate change adaptation in Himalaya
Smallholder farmers’ responses to the climate-induced agricultural changes are not uniform but rather diverse, as response adaptation strategies are embedded in the heterogonous agronomic, social, economic, and institutional conditions. There is an urgent need to understand the diversity within the farming households, identify the main drivers and understand its relationship with household adaptation strategies. Typology construction provides an efficient method to understand farmer diversity by delineating groups with common characteristics. In the present study, based in the Uttarakhand state of Indian Western Himalayas, five farmer types were identified on the basis of resource endowment and agriculture orientation characteristics. Factor analysis followed by sequential agglomerative hierarchial and K-means clustering was use to delineate farmer types. Examination of adaptation strategies across the identified farmer types revealed that mostly contrasting and type-specific bundle of strategies are adopted by farmers to ensure livelihood security. Our findings show that strategies that incurred high investment, such as infrastructural development, are limited to high resource-endowed farmers. In contrast, the low resourced farmers reported being progressively disengaging with farming as a livelihood option. Our results suggest that the proponents of effective adaptation policies in the Himalayan region need to be cognizant of the nuances within the farming communities to capture the diverse and multiple adaptation needs and constraints of the farming households. © 2019, The Author(s).