When the microbiome shapes the host: immune evolution implications for infectious disease

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: This article has no additional data.The microbiome includes both 'mutualist' and 'pathogen' microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests hosts can selectively activate innate immunity upon pathogenic infection, but not mutualist colonization. Another idea posits that hosts can selectively attack pathogens, but not mutualists. Here I review evolutionary principles of microbe recognition and immune activation, and reflect on newly observed immune effector-microbe specificity perhaps supporting the latter idea. Recent work in Drosophila has found a surprising importance for single antimicrobial peptides in combatting specific ecologically relevant microbes. The developing picture suggests these effectors have evolved for this purpose. Other defence responses like reactive oxygen species bursts can also be uniquely effective against specific microbes. Signals in other model systems including nematodes, Hydra, oysters, and mammals, suggest that effector-microbe specificity may be a fundamental principle of host-pathogen interactions. I propose this effector-microbe specificity stems from weaknesses of the microbes themselves: if microbes have intrinsic weaknesses, hosts can evolve effectors that exploit those weaknesses. I define this host-microbe relationship as 'the Achilles principle of immune evolution'. Incorporating this view helps interpret why some host-microbe interactions develop in a coevolutionary framework (e.g. Red Queen dynamics), or as a one-sided evolutionary response. This clarification should be valuable to better understand the principles behind host susceptibilities to infectious diseases. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.Swiss National Science Foundatio

New insights on Drosophila antimicrobial peptide function in host defense and beyond

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Since the first animal antimicrobial peptides (AMPs) were discovered in insects, Drosophila melanogaster has emerged as a powerful model for their characterization. Drosophila AMPs have been used extensively to monitor the activity of the Toll and Imd NF-κB pathways, but little was known of their precise functions. In this review, we summarize recent findings on the function of Drosophila AMPs not only for antimicrobial defense, but also in the gut, tumor control, and neurology. The integration of these new studies allows a new framework to be drawn that explains how AMPs can contribute simultaneously to microbe killing whilst also regulating important host cellular functions. These functions require that AMPs target not only negatively charged microbes but also aberrant host cells.SNF SinergiaNovarti

Three‐dimensional, multispecies, high spatial resolution MHD studies of the solar wind interaction with Mars

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95232/1/jgra17355.pd

Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this recordData availability: Raw data and analysis scripts and outputs are available in the supplementary data files included with this manuscriptAntimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, we reveal the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments.Swiss National Science Foundation (SNSF)SinergiaNovartis Foundatio

An Ultra-High Discrimination Y Chromosome Short Tandem Repeat Multiplex DNA Typing System

In forensic casework, Y chromosome short tandem repeat markers (Y-STRs) are often used to identify a male donor DNA profile in the presence of excess quantities of female DNA, such as is found in many sexual assault investigations. Commercially available Y-STR multiplexes incorporating 12–17 loci are currently used in forensic casework (Promega's PowerPlex® Y and Applied Biosystems' AmpFlSTR® Yfiler®). Despite the robustness of these commercial multiplex Y-STR systems and the ability to discriminate two male individuals in most cases, the coincidence match probabilities between unrelated males are modest compared with the standard set of autosomal STR markers. Hence there is still a need to develop new multiplex systems to supplement these for those cases where additional discriminatory power is desired or where there is a coincidental Y-STR match between potential male participants. Over 400 Y-STR loci have been identified on the Y chromosome. While these have the potential to increase the discrimination potential afforded by the commercially available kits, many have not been well characterized. In the present work, 91 loci were tested for their relative ability to increase the discrimination potential of the commonly used ‘core’ Y-STR loci. The result of this extensive evaluation was the development of an ultra high discrimination (UHD) multiplex DNA typing system that allows for the robust co-amplification of 14 non-core Y-STR loci. Population studies with a mixed African American and American Caucasian sample set (n = 572) indicated that the overall discriminatory potential of the UHD multiplex was superior to all commercial kits tested. The combined use of the UHD multiplex and the Applied Biosystems' AmpFlSTR® Yfiler® kit resulted in 100% discrimination of all individuals within the sample set, which presages its potential to maximally augment currently available forensic casework markers. It could also find applications in human evolutionary genetics and genetic genealogy

Demonstration of entanglement-by-measurement of solid state qubits

Projective measurements are a powerful tool for manipulating quantum states. In particular, a set of qubits can be entangled by measurement of a joint property such as qubit parity. These joint measurements do not require a direct interaction between qubits and therefore provide a unique resource for quantum information processing with well-isolated qubits. Numerous schemes for entanglement-by-measurement of solid-state qubits have been proposed, but the demanding experimental requirements have so far hindered implementations. Here we realize a two-qubit parity measurement on nuclear spins in diamond by exploiting the electron spin of a nitrogen-vacancy center as readout ancilla. The measurement enables us to project the initially uncorrelated nuclear spins into maximally entangled states. By combining this entanglement with high-fidelity single-shot readout we demonstrate the first violation of Bells inequality with solid-state spins. These results open the door to a new class of experiments in which projective measurements are used to create, protect and manipulate entanglement between solid-state qubits.Comment: 6 pages, 4 figure