A major lineage of non-tailed dsDNA viruses as unrecognized killers of marine bacteria.

The most abundant viruses on Earth are thought to be double-stranded DNA (dsDNA) viruses that infect bacteria. However, tailed bacterial dsDNA viruses (Caudovirales), which dominate sequence and culture collections, are not representative of the environmental diversity of viruses. In fact, non-tailed viruses often dominate ocean samples numerically, raising the fundamental question of the nature of these viruses. Here we characterize a group of marine dsDNA non-tailed viruses with short 10-kb genomes isolated during a study that quantified the diversity of viruses infecting Vibrionaceae bacteria. These viruses, which we propose to name the Autolykiviridae, represent a novel family within the ancient lineage of double jelly roll (DJR) capsid viruses. Ecologically, members of the Autolykiviridae have a broad host range, killing on average 34 hosts in four Vibrio species, in contrast to tailed viruses which kill on average only two hosts in one species. Biochemical and physical characterization of autolykiviruses reveals multiple virion features that cause systematic loss of DJR viruses in sequencing and culture-based studies, and we describe simple procedural adjustments to recover them. We identify DJR viruses in the genomes of diverse major bacterial and archaeal phyla, and in marine water column and sediment metagenomes, and find that their diversity greatly exceeds the diversity that is currently captured by the three recognized families of such viruses. Overall, these data suggest that viruses of the non-tailed dsDNA DJR lineage are important but often overlooked predators of bacteria and archaea that impose fundamentally different predation and gene transfer regimes on microbial systems than on tailed viruses, which form the basis of all environmental models of bacteria-virus interactions.

Resolving the structure of phage-bacteria interactions in the context of natural diversity.

Microbial communities are shaped by viral predators. Yet, resolving which viruses (phages) and bacteria are interacting is a major challenge in the context of natural levels of microbial diversity. Thus, fundamental features of how phage-bacteria interactions are structured and evolve in the wild remain poorly resolved. Here we use large-scale isolation of environmental marine Vibrio bacteria and their phages to obtain estimates of strain-level phage predator loads, and use all-by-all host range assays to discover how phage and host genomic diversity shape interactions. We show that lytic interactions in environmental interaction networks (as observed in agar overlay) are sparse-with phage predator loads being low for most bacterial strains, and phages being host-strain-specific. Paradoxically, we also find that although overlap in killing is generally rare between tailed phages, recombination is common. Together, these results suggest that recombination during cryptic co-infections is an important mode of phage evolution in microbial communities. In the development of phages for bioengineering and therapeutics it is important to consider that nucleic acids of introduced phages may spread into local phage populations through recombination, and that the likelihood of transfer is not predictable based on lytic host range.

Orbitofrontal cortex governs working memory for temporal order.

How do we think about time? Converging lesion and neuroimaging evidence indicates that orbitofrontal cortex (OFC) supports the encoding and retrieval of temporal context in long-term memory1, which may contribute to confabulation in individuals with OFC damage2. Here, we reveal that OFC damage diminishes working memory for temporal order, that is, the ability to disentangle the relative recency of events as they unfold. OFC lesions reduced working memory for temporal order but not spatial position, and individual deficits were commensurate with lesion size. Comparable effects were absent in patients with lesions restricted to lateral prefrontal cortex (PFC). Based on these findings, we propose that OFC supports understanding of the order of events. Well-documented behavioral changes in individuals with OFC damage2 may relate to impaired temporal-order understanding.

Gender bias in academia: A lifetime problem that needs solutions.

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

Topological analysis reveals state transitions in human gut and marine bacterial communities.

Microbiome dynamics influence the health and functioning of human physiology and the environment and are driven in part by interactions between large numbers of microbial taxa, making large-scale prediction and modeling a challenge. Here, using topological data analysis, we identify states and dynamical features relevant to macroscopic processes. We show that gut disease processes and marine geochemical events are associated with transitions between community states, defined as topological features of the data density. We find a reproducible two-state succession during recovery from cholera in the gut microbiomes of multiple patients, evidence of dynamic stability in the gut microbiome of a healthy human after experiencing diarrhea during travel, and periodic state transitions in a marine Prochlorococcus community driven by water column cycling. Our approach bridges small-scale fluctuations in microbiome composition and large-scale changes in phenotype without details of underlying mechanisms, and provides an assessment of microbiome stability and its relation to human and environmental health.

Characterization of antimicrobial peptide activity by electrochemical impedance spectroscopy.

Electrochemical impedance spectroscopy performed on surface-supported bilayer membranes allows for the monitoring of changes in membrane properties, such as thickness, ion permeability, and homogeneity, after exposure to antimicrobial peptides (AMPs). We show that two model cationic peptides, very similar in sequence but different in activity, induce dramatically different changes in membrane properties as probed by impedance spectroscopy. Moreover, the impedance results excluded the "barrel-stave" and the "toroidal pore" models of AMP mode of action, and are more consistent with the "carpet" and the "detergent" models. The impedance data provide important new insights about the kinetics and the scale of the peptide action which currently are not addressed by the "carpet" and the "detergent" models. The method presented not only provides additional information about the mode of action of a particular AMP, but offers a means of characterizing AMP activity in reproducible, well-defined quantitative terms.

Tumour-stromal interactions generate emergent persistence in collective cancer cell migration.

Cancer cell collective migration is a complex behaviour leading to the invasion of cancer cells into surrounding tissue, often with the aid of stromal cells in the microenvironment, such as macrophages or fibroblasts. Although tumour-tumour and tumour-stromal intercellular signalling have been shown to contribute to cancer cell migration, we lack a fundamental theoretical understanding of how aggressive invasion emerges from the synergy between these mechanisms. We use a computational self-propelled particle model to simulate intercellular interactions between co-migrating tumour and stromal cells and study the emergence of collective movement. We find that tumour-stromal interaction increases the cohesion and persistence of migrating mixed tumour-stromal cell clusters in a noisy and unbounded environment, leading to increased cell cluster size and distance migrated by cancer cells. Although environmental constraints, such as vasculature or extracellular matrix, influence cancer migration in vivo, our model shows that cell-cell interactions are sufficient to generate cohesive and persistent movement. From our results, we conclude that inhibition of tumour-stromal intercellular signalling may present a viable therapeutic target for disrupting collective cancer cell migration.