The Neurosphere Simulator: An educational online tool for modeling neural stem cell behavior and tissue growth.

Until very recently, distance education, including digital science labs, served a rather small portion of postsecondary students in the United States and many other countries. This situation has, however, dramatically changed in 2020 in the wake of the COVID-19 pandemic, which forced colleges to rapidly transit from face-to-face instructions to online classes. Here, we report the development of an interactive simulator that is freely available on the web (http://neurosphere.cos.northeastern.edu/) for teaching lab classes in developmental biology. This simulator is based on cellular automata models of neural-stem-cell-driven tissue growth in the neurosphere assay. By modifying model parameters, users can explore the role in tissue growth of several developmental mechanisms, such as regulation of mitosis or apoptotic cell death by contact inhibition. Besides providing an instantaneous animation of the simulated development of neurospheres, the Neurosphere Simulator tool offers also the possibility to download data for detailed analysis. The simulator function is complemented by a tutorial that introduces students to computational modeling of developmental processes.

The people behind the papers - Andrew Economou and Jeremy Green.

Interacting morphogens produce periodic patterns in developing tissues. Such patterning can be modelled as reaction-diffusion (RD) processes (as originally formulated by Alan Turing), and although these models have been developed and refined over the years, they often tend to oversimplify biological complexity by restricting the number of interacting morphogens. A new paper in Development reports how perturbation analysis can guide multi-morphogen modelling of the striped patterning the roof of the mouse mouth. To hear more about the story, we caught up with first author Andrew Economou and his former supervisor Jeremy Green, Professor of Developmental Biology at King's College, London.

Pathologic Lesions of the Budgett Frog (Lepidobatrachus laevis), an Emerging Laboratory Animal Model.

Lepidobatrachus laevis, commonly called the Budgett frog, is a member of the horned frog family (Ceratophryidae), which has become increasingly popular among amphibian hobbyists. L. laevis is also used in biologic research on embryonic development, providing a novel model species for the study of organogenesis, regeneration, evolution, and biologic scaling. However, little scientific literature details disease processes or histologic lesions in this species. Our objective was to describe spontaneous pathologic lesions in L. laevis to identify disease phenotypes. We performed a retrospective analysis of 14 captive L. laevis frogs (wild-caught and captive-bred), necropsied at the NC State University College of Veterinary Medicine between 2008 and 2018. The majority of frogs exhibited renal changes, including varying combinations of tubular epithelial binucleation, karyomegaly, and cytoplasmic vacuolation; polycystic kidney disease; and renal carcinoma. Many of the renal changes are reminiscent of a condition described in Japanese (Bufo japonicus) and Chinese (Bufo raddei) toad hybrids that progresses from tubular epithelial atypia and tubular dilation to polycystic kidney disease to renal carcinoma. A second common finding was variably sized, randomly distributed bile duct clusters (biliary proliferation). Other noteworthy findings included regional or generalized edema, intestinal adenocarcinoma, aspiration pneumonia, and parasitism. This retrospective analysis is the first description of histologic lesions identified in captive L. laevis populations, providing new insight into spontaneous disease processes occurring in this species for use in disease diagnosis and clinical management.

Why achieving gender equality is of fundamental importance to improve the health and well-being of future generations: a DOHaD perspective.

Despite progress in gender equality, women continue to be disadvantaged compared with men. Worldwide, women are more often confronted with poverty, violence, and mental health problems, and they have less access to food and education. All these factors do not only affect women themselves, but also have a negative impact on the child's early environment and impair its early development, thereby reducing the health and well-being of future generations. Framing gender equality as a women's issue fails to highlight the importance of gender equality for the health and well-being of the next generation. As a scientific community investigating early human development and health, we have failed to fully recognize and underscore the importance of gender equality in achieving the best possible start for every child. If women and men had equal rights and opportunities, their children would be more likely to reach their full potential which would improve the health and well-being of future generations. Our studies and interventions have not fully taken into account the complexity of gender inequality and women's disadvantaged positions in society. We need better insight into the complex adaptive interactions between various societal and human factors contributing to gender inequality and find approaches that take this complexity into account. If we want DOHaD science to have societal impact, we should strive beyond gender equality for gender equity and help women achieve equal rights and opportunities. We need to work with public health professionals, human rights activists, and policymakers to gauge the importance of gender equality. After all, gender equality is not only a fundamental human right, but also a necessary foundation for healthier future generations.

Adapting a Plant Tissue Model to Animal Development: Introducing Cell Sliding into VirtualLeaf.

Cell-based, mathematical modeling of collective cell behavior has become a prominent tool in developmental biology. Cell-based models represent individual cells as single particles or as sets of interconnected particles and predict the collective cell behavior that follows from a set of interaction rules. In particular, vertex-based models are a popular tool for studying the mechanics of confluent, epithelial cell layers. They represent the junctions between three (or sometimes more) cells in confluent tissues as point particles, connected using structural elements that represent the cell boundaries. A disadvantage of these models is that cell-cell interfaces are represented as straight lines. This is a suitable simplification for epithelial tissues, where the interfaces are typically under tension, but this simplification may not be appropriate for mesenchymal tissues or tissues that are under compression, such that the cell-cell boundaries can buckle. In this paper, we introduce a variant of VMs in which this and two other limitations of VMs have been resolved. The new model can also be seen as on off-the-lattice generalization of the Cellular Potts Model. It is an extension of the open-source package VirtualLeaf, which was initially developed to simulate plant tissue morphogenesis where cells do not move relative to one another. The present extension of VirtualLeaf introduces a new rule for cell-cell shear or sliding, from which cell rearrangement (T1) and cell extrusion (T2) transitions emerge naturally, allowing the application of VirtualLeaf to problems of animal development. We show that the updated VirtualLeaf yields different results than the traditional vertex-based models for differential adhesion-driven cell sorting and for the neighborhood topology of soft cellular networks.

Cell migration analysis: A low-cost laboratory experiment for cell and developmental biology courses using keratocytes from fish scales.

Cell and developmental processes are complex, and profoundly dependent on spatial relationships that change over time. Innovative educational or teaching strategies are always needed to foster deep comprehension of these processes and their dynamic features. However, laboratory exercises in cell and developmental biology at the undergraduate level do not often take into account the time dimension. In this article, we provide a laboratory exercise focused in cell migration, aiming to stimulate thinking in time and space dimensions through a simplification of more complex processes occurring in cell or developmental biology. The use of open-source tools for the analysis, as well as the whole package of raw results (available at http://github.com/danielprieto/keratocyte) make it suitable for its implementation in courses with very diverse budgets. Aiming to facilitate the student's transition from science-students to science-practitioners we propose an exercise of scientific thinking, and an evaluation method. This in turn is communicated here to facilitate the finding of common caveats and weaknesses in the process of producing simple scientific communications describing the results achieved. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):475-482, 2017.

Geroscience: Addressing the mismatch between its exciting research opportunities, its economic imperative and its current funding crisis.

There is at present a huge disconnect between levels of funding for basic research on fundamental mechanisms of biological aging and, given demographic projections, the anticipated enormous social and economic impacts of a litany of chronic diseases for which aging is by far the major risk factor: One valuable approach, recently instigated by Felipe Sierra & colleagues at the US National Institute on Aging, is the development of a Geroscience Interest Group among virtually all of the NIH institutes. A complementary approach would be to seek major escalations of private funding. The American Federation for Aging Research, the Paul Glenn Foundation and the Ellison Medical Foundation pioneered efforts by the private sector to provide substantial supplements to public sources of funding. It is time for our community to organize efforts towards the enhancements of such crucial contributions, especially in support of the emerging generation of young investigators, many of whom are leaving our ranks to seek alternative employment. To do so, we must provide potential donors with strong economic, humanitarian and scientific rationales. An initial approach to such efforts is briefly outlined in this manuscript as a basis for wider discussions within our community.

A quantitative weight of evidence methodology for the assessment of reproductive and developmental toxicity and its application for classification and labeling of chemicals.

Hazard assessment of chemicals usually applies narrative assessments with a number of weaknesses. Therefore, application of weight of evidence (WoE) approaches are often mandated but guidance to perform a WoE assessment is lacking. This manuscript describes a quantitative WoE (QWoE) assessment for reproductive toxicity data and its application for classification and labeling (C&L). Because C&L criteria are based on animal studies, the scope is restricted to animal toxicity data. The QWoE methodology utilizes numerical scoring sheets to assess reliability of a publication and the toxicological relevance of reported effects. Scores are given for fourteen quality aspects, best practice receives the highest score. The relevance/effects scores (0 to four) are adjusted to the key elements of the toxic response for the endpoint and include weighting factors for effects on different levels of the biological organization. The relevance/effects scores are then assessed against the criteria dose-response, magnitude and persistence of effects, consistency of observations with the hypothesis, and relation of effects to human disease. The quality/reliability scores and the relevance/effect scores are then multiplied to give a numerical strength of evidence for adverse effects. This total score is then used to assign the chemical to the different classes employed in classification.

An interview with Nipam Patel.

Nipam Patel is a developmental biologist based at the University of California, Berkeley, USA, where he uses a variety of organisms to study the evolution of developmental systems, from arthropod body plans to butterfly colouration. We asked him about his career and scientific interests, his role as an editor at Development, and his growing butterfly collection.

Budgett's frog (Lepidobatrachus laevis): A new amphibian embryo for developmental biology.

The large size and rapid development of amphibian embryos has facilitated ground-breaking discoveries in developmental biology. Here, we describe the embryogenesis of the Budgett's frog (Lepidobatrachus laevis), an unusual species with eggs that are over twice the diameter of laboratory Xenopus, and embryos that can tolerate higher temperatures to develop into a tadpole four times more rapidly. In addition to detailing their early development, we demonstrate that, like Xenopus, these embryos are amenable to explant culture assays and can express exogenous transcripts in a tissue-specific manner. Moreover, the steep developmental trajectory and large scale of Lepidobatrachus make it exceptionally well-suited for morphogenesis research. For example, the developing organs of the Budgett's frog are massive compared to those of most model species, and are composed of larger individual cells, thereby affording increased subcellular resolution of early vertebrate organogenesis. Furthermore, we found that complete limb regeneration, which typically requires months to achieve in most vertebrate models, occurs in a matter of days in the Budgett's tadpole, which substantially accelerates the pace of experimentation. Thus, the unusual combination of the greater size and speed of the Budgett's frog model provides inimitable advantages for developmental studies-and a novel inroad to address the mechanisms of spatiotemporal scaling during evolution.

From fetal physiology to gene therapy: it all started in Loma Linda.

Just having finished medical school in the Netherlands, without basically any serious research experience, Lawrence Longo, Gordon Power and Ray Gilbert received this 25 year young man with open arms at the end of July 1977. The Center for Perinatal Biology of Loma Linda University (CPB) would become for the next 3 years not the just the center of my postdoctoral activities, it would also lay the foundation for the following decades. The next paragraphs will describe three key success factors that can be traced back to these formative years that have contributed so much to my professional career.

A developmental systems approach to executive function.

According to recent claims from behavior genetics, executive function (EF) is almost entirely heritable. The implications of this claim are significant, given the importance of EF in academic, social, and psychological domains. This paper critically examines the behavior genetics approach to explaining individual differences in EF and proposes a relational developmental systems model that integrates both biological and social factors in the development of EF and the emergence of individual differences in EF. Problems inherent to behavioral genetics research are discussed, as is neuroscience research that emphasizes the plasticity of the prefrontal cortex. Empirical evidence from research on stress, social interaction, and intervention and training demonstrates that individual differences in EF are experience-dependent. Taken together, these findings challenge the claim that EF is almost entirely genetic but are consistent with an approach that considers biological differences in the context of social interaction.

History, biology, and health inequities: emergent embodied phenotypes and the illustrative case of the breast cancer estrogen receptor.

How we think about biology--in historical, ecological, and societal context--matters for framing causes of and solutions to health inequities. Drawing on new insights from ecological evolutionary developmental biology and ecosocial theory, I question dominant gene-centric and ultimately static approaches to conceptualizing biology, using the example of the breast cancer estrogen receptor (ER). Analyzed in terms of its 4 histories--societal, individual (life course), tumor (cellular pathology), and evolutionary--the ER is revealed as a flexible characteristic of cells, tumors, individuals, and populations, with magnitudes of health inequities tellingly changing over time. This example suggests our science will likely be better served by conceptualizing disease and its biomarkers, along with changing magnitudes of health inequities, as embodied history--that is, emergent embodied phenotype, not innate biology.