Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy). Advancing the food system transformation to healthy, sustainable diets transcends the personal control of engaging consumers. The challenge for science is to scale-up, to become more interdisciplinary, and to engage with policymakers and food system actors. This will provide the evidential basis to shift from the current narrative of price, convenience, and taste to one of health, sustainability, and equity. The breaches of planetary boundaries and the environmental and health costs of the food system can no longer be considered externalities. However, conflicting interests and traditions frustrate effective changes in the human-made food system. Public and private stakeholders must embrace social inclusiveness and include the role and accountability of all food system actors from the microlevel to the macrolevel. To achieve this food transformation, a new "social contract," led by governments, is needed to redefine the economic and regulatory power balance between consumers and (inter)national food system actors.

Background: Eating habits must change substantially in order to address the urgent societal challenges of per-sonal, public and planetary health. Research surrounding various facets of the dietary transition remains siloed, hindering breakthroughs.Scope and approach: We argue the scientific case for transdisciplinary research centered around the transition to healthy, sustainable, and acceptable diets. This transition requires tackling the broad societal challenges of engaging consumers in the diet transition, improving nutritional health and achieving environmental sustain -ability of foods and food systems.Key findings: The crucial synergies and trade-offs from addressing single challenges in isolation are discussed, as well as obstacles when considering the collaboration between the multiple scientific disciplines concerned with the dietary transition. Currently, interactions between these challenges remain understudied and/or ambiguous, in part due to a lack of interoperable data and standards. Intersectional research entry points acting at the intersection of the three challenges are explored: food taste and texture reformulation, food pricing strategies and food literacy. The implementation of such cross-cutting interventions urgently requires both the generation of new data and exploitation of the breadth of existing data. Researchers must therefore be facilitated to find, access and use interoperable data to model and measure food intake and all its determinants.Conclusions: The dietary transition requires underpinning by a research infrastructure that supports access to transdisciplinary data, facilities and research tools, alongside training and capacity building. Filling these unmet data, tools and training needs is the first step towards delivering breakthrough innovations to foods and food environments, mobilizing consumers to engage in the dietary transition.

The relation among the various causal factors of obesity is not well understood, and there remains a lack of viable data to advance integrated, systems models of its etiology. The collection of big data has begun to allow the exploration of causal associations between behavior, built environment, and obesity-relevant health outcomes. Here, the traditional epidemiologic and emerging big data approaches used in obesity research are compared, describing the research questions, needs, and outcomes of 3 broad research domains: eating behavior, social food environments, and the built environment. Taking tangible steps at the intersection of these domains, the recent European Union project "BigO: Big data against childhood obesity" used a mobile health tool to link objective measurements of health, physical activity, and the built environment. BigO provided learning on the limitations of big data, such as privacy concerns, study sampling, and the balancing of epidemiologic domain expertise with the required technical expertise. Adopting big data approaches will facilitate the exploitation of data concerning obesity-relevant behaviors of a greater variety, which are also processed at speed, facilitated by mobile-based data collection and monitoring systems, citizen science, and artificial intelligence. These approaches will allow the field to expand from causal inference to more complex, systems-level predictive models, stimulating ambitious and effective policy interventions.

Malnutrition in an obese world was the fitting title of the 13th Federation of European Nutrition Societies (FENS) conference held in October 2019. Many individuals do not eat a healthy, well-balanced diet, and this is now understood to be a major driver of increased disease risk and illness. Moreover, both our current eating patterns and the food system as a whole are environmentally unsustainable, threatening the planetary systems we depend on for survival. As we attempt to feed a growing global population, food systems will increasingly be confronted with their environmental impacts, with the added challenge of climate change-induced threats to food production. As we move into the third decade of the twenty-first century, these challenges demand that the nutrition research community reconsider its scope, concepts, methods, and societal role. At a pre-meeting workshop held at the FENS conference, over 70 researchers active in the field explored ways to advance the discipline’s capacity to address cross-cutting issues of personal, public and planetary health. Using the world cafe method, four themed discussion tables explored (a) the breadth of scientific domains needed to meet the current challenges, (b) the nature and definition of the shifting concepts in nutrition sciences, (c) the next-generation methods required and (d) communication and organisational challenges and opportunities. As a follow-up to earlier work [1], here we report the highlights of the discussions, and propose the next steps to advance responsible research and innovation in the domain of nutritional science.

Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.

Specialized areas in the vertebrate retina are critical for high-acuity vision, yet the molecular mechanisms driving the development of high-acuity areas (HAAs) remain largely unknown. In Developmental Cell, da Silva and Cepko (2017) show that restricted degradation of retinoic acid and elevated FGF8 signaling give rise to the chick HAA.

The visual system consists of two major subsystems, image-forming circuits that drive conscious vision and non-image-forming circuits for behaviors such as circadian photoentrainment. While historically considered non-overlapping, recent evidence has uncovered crosstalk between these subsystems. Here, we investigated shared developmental mechanisms. We revealed an unprecedented role for light in the maturation of the circadian clock and discovered that intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for this refinement process. In addition, ipRGCs regulate retinal waves independent of light, and developmental ablation of a subset of ipRGCs disrupts eye-specific segregation of retinogeniculate projections. Specifically, a subset of ipRGCs, comprising ~200 cells and which project intraretinally and to circadian centers in the brain, are sufficient to mediate both of these developmental processes. Thus, this subset of ipRGCs constitute a shared node in the neural networks that mediate light-dependent maturation of the circadian clock and light-independent refinement of retinogeniculate projections.

Previous studies have demonstrated an age related decline in the size of the neural stem cell (NSC) pool and a decrease in neural progenitor cell proliferation, however, the mechanisms underlying these changes are unclear. In contrast to previous reports, we report that the numbers of NSCs is unchanged in the old age subependyma and the apparent loss is because of reduced proliferative potential in the aged stem cell niche. Transplantation studies reveal that the proliferation kinetics and migratory behavior of neural precursor cells are dependent on the age of the host animal and independent of the age of the donor cells suggesting that young and old age neural precursors are not intrinsically different. Factors from the young stem cell niche rescue the numbers of NSC colonies derived from old age subependyma and enhance progenitor cell proliferation in vivo in old age mice. Finally, we report a loss of Wnt signaling in the old age stem cell niche that underlies the lack of expansion of the NSC pool after stroke.

In the developing nervous system, cell diversification depends on the ability of neural progenitor cells to divide asymmetrically to generate daughter cells that acquire different identities. While much work has recently focused on the mechanisms controlling self-renewing asymmetric divisions producing a differentiating daughter and a progenitor, little is known about mechanisms regulating how distinct differentiating cell types are produced at terminal divisions. Here we study the role of the endocytic adaptor protein Numb in the developing mouse retina. Using clonal numb inactivation in retinal progenitor cells (RPCs), we show that Numb is required for normal cell-cycle progression at early stages, but is dispensable for the production of self-renewing asymmetric cell divisions. At late stages, however, Numb is no longer required for cell-cycle progression, but is critical for the production of terminal asymmetric cell divisions. In the absence of Numb, asymmetric terminal divisions that generate a photoreceptor and a non-photoreceptor cell are decreased in favor of symmetric terminal divisions generating two photoreceptors. Using live imaging in retinal explants, we show that a Numb fusion protein is asymmetrically inherited by the daughter cells of some late RPC divisions. Together with our finding that Numb antagonizes Notch signaling in late-stage RPCs, and that blocking Notch signaling in late RPCs almost completely abolishes the generation of terminal asymmetric divisions, these results suggest a model in which asymmetric inheritance of Numb in sister cells of terminal divisions might create unequal Notch activity, which in turn drives the production of terminal asymmetric divisions.

A number of studies support the conclusion that single CaV channels Ca2+ nanodomains gate molecular signaling pathways. Thus, at presynaptic terminals single CaV2.2 channels trigger fusion of synaptic vesicle (SVs) by saturating a nearby calcium sensor.2 It is generally accepted that CaV1, CaV2, and CaV3 families (L, N and T, respectively) exhibit a decreasing order of single channel conductance.1 Since nanodomain dimensions are proportional to single channel current amplitude (i), high-conductance L type channels would be expected to be favored over the intermediate conductance N-type. Since the L>N>T hierarchy was determined with high Ba2+EXT, we tested the idea that this sequence may differ at physiological Ca2+EXT. We recorded i values for all three CaV families across a broad range of Ca2+EXT, spanning the physiological range. We focused on i-65mV to avoid non-linear current-to-voltage relationship complications and for direct relevance to the gating of synaptic transmission.3 A CaV2.2>CaV1>CaV3.2 hierarchy was determined for i-65mV at 1-2 mM Ca2+EXT. Mathematical modeling predicts that the CaV2.2 Ca2+ nanodomain is ∼25% more extensive than that generated by CaV1. We also calculated single channel 'SV fusion' domains, defined as the radii where the channel would saturate ≥50% of 5-binding site calcium sensors. With a sensor binding affinity of 10μM a single CaV2.2 can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.4 These findings may explain why CaV2 family channels are preferred for transmitter release site gating. 1. Fox AP, Nowycky MC & Tsien RW JP 394:173(1987). 2. Stanley EF Neuron 11:1007(1993). 3. Llinas RR, Sugimori M & Simon SM PNAS 79:2415(1982). 4. Weber AM,∗ Wong FK∗, Tufford AR, Schlichter LC, Matveev V & Stanley EF Nature Neurosci in press (2010).

The established conductance hierarchy of voltage-gated calcium channels, where conductance of Ca V 1 is greater than Ca V 2, which is in turn greater than Ca V 3, was determined using nonphysiological divalent ion concentrations. Weber et al . find that Ca V 2.2 conductance is greater than that of Ca V 1 and Ca V 3 and investigate implications for Ca 2+ nanodomain signaling.