The rise of multicellularity represents a major evolutionary transition and it occurred independently in multiple eukaryote clades. Although simple multicellular organisms may have evolved in the Mesoproterozoic Era or even earlier, complex multicellular eukaryotes began to diversify only in the Ediacaran Period, just before the Cambrian explosion. Thus, the Ediacaran fossil record can provide key paleontological evidence about the early radiation of multicellular eukaryotes that ultimately culminated in the Cambrian explosion. The Ediacaran Weng'an biota in South China hosts exceptionally preserved eukaryote fossils, including various acanthomorphic acritarchs, pseudoparenchymatous thalli, tubular microfossils, and spheroidal fossils such as Megasphaera, Helicoforamina, Spiralicellula, and Caveasphaera. Many of these fossils have been interpreted as multicellular eukaryotes, although alternative interpretations have also been proposed. In this review, we critically examine these various interpretations, focusing particularly on Megasphaera, which has been variously interpreted as a sulfur-oxidizing bacterium, a unicellular protist, a mesomycetozoean-like holozoan, a volvocine green alga, a stem-group animal, or a crown-group animal. We conclude that Megasphaera is a multicellular eukaryote with evidence for cell-to-cell adhesion, a flexible membrane unconstrained by a rigid cell wall, spatial cellular differentiation, germ–soma separation, and programmed cell death. These features are inconsistent with the bacterium, unicellular protist, and mesomycetozoean-like holozoan interpretations. Thus, the surviving hypotheses, particularly the stem-group animal and algal interpretations, should be further tested with additional evidence. The Weng'an biota also hosts cellularly differentiated pseudoparenchymatous thalli with specialized reproductive structures indicative of an affinity with florideophyte red algae. The other Weng'an fossils reviewed here may also be multicellular eukaryotes, although direct cellular evidence is lacking in some and phylogenetic affinities are poorly constrained in others. The Weng'an biota offers many research opportunities to resolve the life histories and phylogenetic diversity of early multicellular eukaryotes and to illuminate the evolutionary prelude to the Cambrian explosion.

Atlases provide a framework for spatially mapping information from diverse sources into a common reference space. Specifically, brain atlases allow annotation of gene expression, cell morphology, connectivity, and activity. In larval zebrafish, advances in genetics, imaging, and computational methods now allow the collection of such information brain-wide. However, due to technical considerations, disparate datasets may use different references and may not be aligned to the same coordinate space. Two recent larval zebrafish atlases exemplify this problem: Z-Brain, containing gene expression, neural activity, and neuroanatomical segmentations, was acquired using immunohistochemical stains, while the Zebrafish Brain Browser (ZBB) was constructed from live scans of fluorescent reporters in transgenic larvae. Although different references were used, the atlases included several common transgenic patterns that provide potential “bridges” for transforming each into the other's coordinate space. We tested multiple bridging channels and registration algorithms and found that the symmetric diffeomorphic normalization algorithm improved live brain registration precision while better preserving cell morphology than B-spline-based registrations. Symmetric diffeomorphic normalization also corrected for tissue distortion introduced during fixation. Multi-reference channel optimization provided a transformation that enabled Z-Brain and ZBB to be co-aligned with precision of approximately a single cell diameter and minimal perturbation of cell and tissue morphology. Finally, we developed software to visualize brain regions in 3 dimensions, including a virtual reality neuroanatomy explorer. This study demonstrates the feasibility of integrating whole brain datasets, despite disparate reference templates and acquisition protocols, when sufficient information is present for bridging. Increased accuracy and interoperability of zebrafish digital brain atlases will facilitate neurobiological studies.

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Epstein-Barr virus (EBV) is an important human pathogen that establishes a lifelong persistent infection and for which no precise animal model exists. In this paper we describe in detail an agentbased model and computer simulation of EBV infection. Agents representing EBV and sets of B and T lymphocytes move and interact on a three-dimensional grid approximating Waldeyer's ring, together with abstract compartments for lymph and blood. The simulation allows us to explore the development and resolution of virtual infections in a manner not possible in actual human experiments. Specifically, we identify parameters capable of inducing clearance, persistent infection, or death.

Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines. Lines labeling neurons of interest can be identified using a web-browser to perform a 3D spatial search (zbbrowser.com). This resource facilitates the design of intersectional genetic experiments and will advance a wide range of precision circuit-mapping studies.