Evaluating how we evaluate

Evaluation of scientific work underlies the process of career advancement in academic science, with publications being a fundamental metric. Many aspects of the evaluation process for grants and promotions are deeply ingrained in institutions and funding agencies and have been altered very little in the past several decades, despite substantial changes that have taken place in the scientific work force, the funding landscape, and the way that science is being conducted. This article examines how scientific productivity is being evaluated, what it is rewarding, where it falls short, and why richer information than a standard curriculum vitae/biosketch might provide a more accurate picture of scientific and educational contributions. The article also explores how the evaluation process exerts a profound influence on many aspects of the scientific enterprise, including the training of new scientists, the way in which grant resources are distributed, the manner in which new knowledge is published, and the culture of science itself.     

Understanding how morphogens work

In this article, we describe the mechanisms by which morphogens in the Xenopus embryo exert their long-range effects. Our results are consistent with the idea that signalling molecules such as activin and the nodal-related proteins traverse responding tissue not by transcytosis or by cytonemes but by movement through the extracellular space. We suggest, however, that additional experiments, involving real-time imaging of morphogens, are required for a real understanding of what influences signalling range and the shape of a morphogen gradient.     

Flies kNOw how to signal

A recent study has discovered a surprising role for nitric oxide in the Drosophila immune response. NO-mediated signaling was implicated in the communication between the site of a localized infection and the major immune organ of the fly, the fat body.     

Confirmation and explaining how possible

Confirmation in evolutionary biology depends on what biologists take to be the genuine rivals. Investigating what constrains the scope of biological possibility provides part of the story: explaining how possible helps determine what counts as a genuine rival and thus informs confirmation. To clarify the criteria for genuine rivalry I distinguish between global and local constraints on biological possibility, and offer an account of how-possibly explanation. To sharpen the connection between confirmation and explaining how possible I discuss the view that formal inquiry can provide a kind of confirmation-theoretic support for evolutionary models, and offer an example of how-possibly explanation interacting with testing practice.     

Understanding how kinase-targeted therapies work

Kinases are central nodes in the cellular pathways that control differentiation, proliferation, apoptosis, motility, and invasion. Most if not all human tumors are thought to bear alterations in one or multiple kinase genes which therefore represent attractive therapeutic targets. Accordingly, intense drug discovery programs have led to the development of clinically effective kinase inhibitors. The road to generate a kinase inhibitor requires, in the initial phase, validation of the oncogenic potential of the corresponding kinase gene in cancer cells. As the catalytic domains of kinases are highly homologous, most inhibitors are predicted to affect multiple kinases. It is therefore important to ensure that a drug of interest acts by direct inhibition of its putative target. To address these issues, we devised a strategy to genetically inactivate the catalytic activity of a given kinase in human cells. This approach generates isogenic cells in which a certain kinase gene is expressed but is devoid of enzymatic activity thus mimicking the chronic pharmacological treatment of cancer cells with a specific and selective kinase inhibitor. This strategy is not limited to kinase genes but could be broadly applicable to any drug/protein combination in which the target enzymatic domain of a gene is known.     

The how and why of adult neurogenesis

Brain plasticity refers to the brain’s ability to change structure and/or function during maturation, learning, environmental challenges, or disease. Multiple and dissociable plastic changes in the adult brain involve many different levels of organization, ranging from molecules to systems, with changes in neural elements occurring hand-in-hand with changes in supportive tissue elements, such as glia cells and blood vessels. There is now substantial evidence indicating that new functional neurons are constitutively generated from endogenous pools of neural stem cells in restricted areas of the mammalian brain, throughout life. So, in addition to all the other known structural changes, entire new neurons can be added to the existing network circuitry. This addition of newborn neurons provides the brain with another tool for tinkering with the morphology of its own functional circuitry. Although the ongoing neurogenesis and migration have been extensively documented in non-mammalian species, its characteristics in mammals have just been revealed and thus several questions remain yet unanswered. Is adult neurogenesis an atavism, an empty-running leftover from evolution? What is adult neurogenesis good for and how does the brain ‘know’ that more neurons are needed? How is this functional demand translated into signals a precursor cell can detect? Adult neurogenesis may represent an adaptive response to challenges imposed by an environment and/or internal state of the animal. To ensure this function, the production, migration, and survival of newborn neurons must be tightly controlled. We attempt to address some of these questions here, using the olfactory bulb as a model system.     

The eggstraordinary story of how life begins

More than 15 years have elapsed since the identification of phospholipase C ζ1 (PLCζ) from a genomic search for mouse testis/sperm‐specific PLCs. This molecule was proposed to represent the sperm factor responsible for the initiation of calcium (Ca²⁺) oscillations required for egg activation and embryo development in mammals. Supporting evidence for this role emerged from studies documenting its expression in all mammals and other vertebrate species, the physiological Ca²⁺ rises induced by injection of its messenger RNA into mammalian and nonmammalian eggs, and the lack of expression in infertile males that fail intracytoplasmic sperm injection. In the last year, genetic animal models have added support to its role as the long sought‐after sperm factor. In this review, we highlight the findings that demonstrated the role of Ca²⁺ as the universal signal of egg activation and the experimental buildup that culminated with the identification of PLCζ as the soluble sperm factor. We also discuss the structural–functional properties that make PLCζ especially suited to evoke oscillations in eggs. Lastly, we examine unresolved aspects of the function and regulation of PLCζ and whether or not it is the only sperm factor in mammalian sperm.     

When, how and how much: Gender-specific resource-use strategies in the dioecious tree Juniperus thurifera

BACKGROUND AND AIMS: In dioecious species male and female plants experience different selective pressures and often incur different reproductive costs. An increase in reproductive investment habitually results in a reduction of the resources available to other demands, such as vegetative growth. Tree-ring growth is an integrative measure that tracks vegetative investment through the plant's entire life span. This allows the study of gender-specific vegetative allocation strategies in dioecious tree species thoughout their life stages. METHODS: Standard dendrochronological procedures were used to measure tree-ring width. Analyses of time-series were made by means of General Mixed Models with correction of autocorrelated values by the use of an autoregressive covariance structure of order one. Bootstrapped correlation functions were used to study the relationship between climate and tree-ring width. KEY RESULTS: Male and female trees invest a similar amount of resources to ring growth during the early life stages of Juniperus thurifera. However, after reaching sexual maturity, tree-ring growth is reduced for both sexes. Furthermore, females experience a significantly stronger reduction in growth than males, which indicates a lower vegetative allocation in females. In addition, growth was positively correlated with precipitation from the current winter and spring in male trees but only to current spring precipitation in females. CONCLUSIONS: Once sexual maturity is achieved, tree rings grow proportionally more in males than in females. Differences in tree-ring growth between the genders could be a strategy to respond to different reproductive demands. Therefore, and responding to the questions of when, how and how much asked in the title, it is shown that male trees invest more resources to growth than female trees only after reaching sexual maturity, and they use these resources in a different temporal way.