FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution

Background: The vertebrate craniofacial skeleton may exhibit anatomical complexity and diversity, but its genesis and evolution can be understood through careful dissection of developmental programs at cellular resolution. Resources are lacking that include introductory overviews of skeletal anatomy coupled with descriptions of craniofacial development at cellular resolution. In addition to providing analytical guidelines for other studies, such an atlas would suggest cellular mechanisms underlying development. Description We present the Fish Face Atlas, an online, 3D-interactive atlas of craniofacial development in the zebrafish Danio rerio. Alizarin red-stained skulls scanned by fluorescent optical projection tomography and segmented into individual elements provide a resource for understanding the 3D structure of the zebrafish craniofacial skeleton. These data provide the user an anatomical entry point to confocal images of Alizarin red-stained zebrafish with transgenically-labelled pharyngeal arch ectomesenchyme, chondrocytes, and osteoblasts, which illustrate the appearance, morphogenesis, and growth of the mandibular and hyoid cartilages and bones, as viewed in live, anesthetized zebrafish during embryonic and larval development. Confocal image stacks at high magnification during the same stages provide cellular detail and suggest developmental and evolutionary hypotheses. Conclusion: The FishFace Atlas is a novel learning tool for understanding craniofacial skeletal development, and can serve as a reference for a variety of studies, including comparative and mutational analyses

RAD marker microarrays enable rapid mapping of zebrafish mutations

A RAD marker microarray was constructed to facilitate rapid genetic mapping of zebrafish mutations and used to localize previously unmapped mutations to genomic regions just a few centiMorgans in length

Chemical biology in the embryo: In situ imaging of sulfur biochemistry in normal and proteoglycan-deficient cartilage matrix

© 2016 American Chemical Society. Proteoglycans (PGs) are heavily glycosylated proteins that play major structural and biological roles in many tissues. Proteoglycans are abundant in cartilage extracellular matrix; their loss is a main feature of the joint disease osteoarthritis. Proteoglycan function is regulated by sulfation-sulfate ester formation with specific sugar residues. Visualization of sulfation within cartilage matrix would yield vital insights into its biological roles. We present synchrotron-based X-ray fluorescence imaging of developing zebrafish cartilage, providing the first in situ maps of sulfate ester distribution. Levels of both sulfur and sulfate esters decrease as cartilage develops through late phase differentiation (maturation or hypertrophy), suggesting a functional link between cartilage matrix sulfur content and chondrocyte differentiation. Genetic experiments confirm that sulfate ester levels were due to cartilage proteoglycans and support the hypothesis that sulfate ester levels regulate chondrocyte differentiation. Surprisingly, in the PG synthesis mutant, the total level of sulfur was not significantly reduced, suggesting sulfur is distributed in an alternative chemical form during lowered cartilage proteoglycan production. Fourier transform infrared imaging indicated increased levels of protein in the mutant fish, suggesting that this alternative sulfur form might be ascribed to an increased level of protein synthesis in the mutant fish, as part of a compensatory mechanism

Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes

Phenotypes resulting from mutations in genetic model organisms can help reveal candidate genes for evolutionarily important phenotypic changes in related taxa. Although testing candidate gene hypotheses experimentally in nonmodel organisms is typically difficult, ontology-driven information systems can help generate testable hypotheses about developmental processes in experimentally tractable organisms. Here, we tested candidate gene hypotheses suggested by expert use of the Phenoscape Knowledgebase, specifically looking for genes that are candidates responsible for evolutionarily interesting phenotypes in the ostariophysan fishes that bear resemblance to mutant phenotypes in zebrafish. For this, we searched ZFIN for genetic perturbations that result in either loss of basihyal element or loss of scales phenotypes, because these are the ancestral phenotypes observed in catfishes (Siluriformes). We tested the identified candidate genes by examining their endogenous expression patterns in the channel catfish, Ictalurus punctatus. The experimental results were consistent with the hypotheses that these features evolved through disruption in developmental pathways at, or upstream of, brpf1 and eda/edar for the ancestral losses of basihyal element and scales, respectively. These results demonstrate that ontological annotations of the phenotypic effects of genetic alterations in model organisms, when aggregated within a knowledgebase, can be used effectively to generate testable, and useful, hypotheses about evolutionary changes in morphology

Mutations in fam20b and xylt1 Reveal That Cartilage Matrix Controls Timing of Endochondral Ossification by Inhibiting Chondrocyte Maturation

Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG)-rich matrix, then undergo a developmental transition, termed “maturation,” when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regulate interactions between chondrocytes and perichondrium, using zebrafish mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which ultimately dictates the timing of perichondral bone development. In a mutagenesis screen, we isolated a class of mutants with decreased cartilage matrix and increased perichondral bone. Positional cloning identified lesions in two genes, fam20b and xylosyltransferase1 (xylt1), both of which encode PG synthesis enzymes. Mutants failed to produce wild-type levels of chondroitin sulfate PGs, which are normally abundant in cartilage matrix, and initiated perichondral bone formation earlier than their wild-type siblings. Primary chondrocyte defects might induce the bone phenotype secondarily, because mutant chondrocytes precociously initiated maturation, showing increased and early expression of such markers as runx2b, collagen type 10a1, and ihh co-orthologs, and ihha mutation suppressed early perichondral bone in PG mutants. Ultrastructural analyses demonstrated aberrant matrix organization and also early cellular features of chondrocyte hypertrophy in mutants. Refining previous in vitro reports, which demonstrated that fam20b and xylt1 were involved in PG synthesis, our in vivo analyses reveal that these genes function in cartilage matrix production and ultimately regulate the timing of skeletal development

Moment Closure - A Brief Review

Moment closure methods appear in myriad scientific disciplines in the modelling of complex systems. The goal is to achieve a closed form of a large, usually even infinite, set of coupled differential (or difference) equations. Each equation describes the evolution of one "moment", a suitable coarse-grained quantity computable from the full state space. If the system is too large for analytical and/or numerical methods, then one aims to reduce it by finding a moment closure relation expressing "higher-order moments" in terms of "lower-order moments". In this brief review, we focus on highlighting how moment closure methods occur in different contexts. We also conjecture via a geometric explanation why it has been difficult to rigorously justify many moment closure approximations although they work very well in practice.Comment: short survey paper (max 20 pages) for a broad audience in mathematics, physics, chemistry and quantitative biolog

Search for CP violation in D+→K−K+π+D^{+} \to K^{-}K^{+}\pi^{+} decays

A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \to K^- K^+\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.

First observation of Bs -> D_{s2}^{*+} X mu nu decays

Using data collected with the LHCb detector in proton-proton collisions at a centre-of-mass energy of 7 TeV, the semileptonic decays Bs -> Ds+ X mu nu and Bs -> D0 K+ X mu nu are detected. Two structures are observed in the D0 K+ mass spectrum at masses consistent with the known D^+_{s1}(2536) and $D^{*+}_{s2}(2573) mesons. The measured branching fractions relative to the total Bs semileptonic rate are B(Bs -> D_{s2}^{*+} X mu nu)/B(Bs -> X mu nu)= (3.3\pm 1.0\pm 0.4)%, and B(Bs -> D_{s1}^+ X munu)/B(Bs -> X mu nu)= (5.4\pm 1.2\pm 0.5)%, where the first uncertainty is statistical and the second is systematic. This is the first observation of the D_{s2}^{*+} state in Bs decays; we also measure its mass and width.Comment: 8 pages 2 figures. Published in Physics Letters

Strength of Social Tie Predicts Cooperative Investment in a Human Social Network

Social networks – diagrams which reflect the social structure of animal groups – are increasingly viewed as useful tools in behavioural ecology and evolutionary biology. Network structure may be especially relevant to the study of cooperation, because the action of mechanisms which affect the cost:benefit ratio of cooperating (e.g. reciprocity, punishment, image scoring) is likely to be mediated by the relative position of actor and recipient in the network. Social proximity could thus affect cooperation in a similar manner to biological relatedness. To test this hypothesis, we recruited members of a real-world social group and used a questionnaire to reveal their network. Participants were asked to endure physical discomfort in order to earn money for themselves and other group members, allowing us to explore relationships between willingness to suffer a cost on another's behalf and the relative social position of donor and recipient. Cost endured was positively correlated with the strength of the social tie between donor and recipient. Further, donors suffered greater costs when a relationship was reciprocated. Interestingly, participants regularly suffered greater discomfort for very close peers than for themselves. Our results provide new insight into the effect of social structure on the direct benefits of cooperation