Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels

Female Aedes aegypti mosquitoes feed on human blood, which they use to develop their eggs. It has been widely noted that some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. Here we tested mosquito attraction to skin odor collected from human subjects and identified people who are exceptionally attractive or unattractive to mosquitoes. Notably, these preferences were stable over several years, indicating consistent longitudinal differences in skin odor between subjects. We carried out gas chromatography/quadrupole time of flight-mass spectrometry to analyze the chemical composition of human skin odor in these subjects and discovered that highly attractive people produce significantly increased levels of carboxylic acids. Consistent with the hypothesis that odor concentration is a major driver of differential attraction, mosquitoes could reliably distinguish a highly attractive human from their weakly attractive counterparts unless we substantially diluted the odor of the most attractive subject. Our work suggests that an increased abundance of mosquito attractants on the preferred subject explains differential attraction, rather than the non-preferred skin odor blend being repellent. Mosquitoes detect carboxylic acids with a large family of odor-gated ion channels encoded by the Ionotropic Receptor gene superfamily. Mutant mosquitoes lacking any of the Ionotropic Receptor (IR) co-receptors Ir8a, Ir25a, and Ir76b, were severely impaired in attraction to human scent but retained the ability to differentiate highly and weakly attractive people. The link between elevated carboxylic acids in mosquito-magnet human skin odor and phenotypes of genetic mutations in carboxylic acid receptors suggests that such compounds contribute to differential mosquito attraction. Understanding why some humans are more attractive than others will provide insights into what skin odorants are most important to the mosquito and could inform the development of more effective repellents.

Neuron and astrocyte aggregation and sorting in three-dimensional neuronal constructs

Aggregation and self-sorting of cells in three dimensional cultures have been described for non-neuronal cells. Despite increased interest in engineered neural tissues for treating brain injury or for modeling neurological disorders in vitro, little data is available on collective cell movements in neuronal aggregates. Migration and sorting of cells may alter these constructs’ morphology and, therefore, the function of their neural circuitry. In this work, linear, adhered rat and human 3D neuronal-astrocyte cultures were developed to enable the study of aggregation and sorting of these cells. An in silico model of the contraction, clustering, and cell sorting in the 3D cultures was also developed. Experiments and computational modeling showed that aggregation was mainly a neuron mediated process, and formation of astrocyte-rich sheaths in 3D cultures depended on differential attraction between neurons and astrocytes. In silico model predicted formation of self-assembled neuronal layers in disk-shaped 3D cultures. Neuronal activity patterns were found to correlate with local morphological differences. This model of neuronal and astrocyte aggregation and sorting may benefit future design of neuronal constructs.

Effects of Carrion Relocation on the Succession of Newly Arriving Adult Necrophilous Insects

Ecological succession of necrophilous insects follows a predictable sequence, related to their differential attraction to changing odor profiles associated with carrion and colonizing insects. However, the dependency of insect arrival on the duration of the carrion’s residency at a location has not been investigated. To assess the fidelity of necrophilous insects to carrion of specific decomposition ages, independent of its location, we monitored the decomposition of neonate pigs in one field and then simultaneously relocated carcasses of different decomposition ages to an ecologically similar but remote field. We examined the effects of decomposition age and relocation on the assembly of the necrophilous insect community, using a novel vented-chamber trap, which excluded all sensory cues except odors. Community composition differed over a 4-d decomposition period, showing that insects were differentially attracted to pigs of different decomposition ages. There was overall concordance between respective decomposition ages in the two fields, with similar relative abundances of taxa before and after transfer. Although different decomposition ages continued to attract different insects, differentiation of the necrophilous insect communities relative to the age of decomposition was less pronounced after transfer. The results of this study demonstrate that translocating a decomposing body to a new, but geographically and ecologically similar location continues the predicted insect succession, albeit with greater variance, based on olfactory cues alone. Several rare taxa were sampled only prior to relocation, including the first documentation of the invasive hairy maggot blow fly, Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae), in central North Carolina.

Chromatin organization by an interplay of loop extrusion and compartmental segregation

Mammalian chromatin is spatially organized at many scales showing two prominent features in interphase: (i) alternating regions (1–10 Mb) of active and inactive chromatin that spatially segregate into different compartments, and (ii) domains (<1 Mb), that is, regions that preferentially interact internally [topologically associating domains (TADs)] and are central to gene regulation. There is growing evidence that TADs are formed by active extrusion of chromatin loops by cohesin, whereas compartmentalization is established according to local chromatin states. Here, we use polymer simulations to examine how loop extrusion and compartmental segregation work collectively and potentially interfere in shaping global chromosome organization. A model with differential attraction between euchromatin and heterochromatin leads to phase separation and reproduces compartmentalization as observed in Hi-C. Loop extrusion, essential for TAD formation, in turn, interferes with compartmentalization. Our integrated model faithfully reproduces Hi-C data from puzzling experimental observations where altering loop extrusion also led to changes in compartmentalization. Specifically, depletion of chromatin-associated cohesin reduced TADs and revealed finer compartments, while increased processivity of cohesin strengthened large TADs and reduced compartmentalization; and depletion of the TAD boundary protein CTCF weakened TADs while leaving compartments unaffected. We reveal that these experimental perturbations are special cases of a general polymer phenomenon of active mixing by loop extrusion. Our results suggest that chromatin organization on the megabase scale emerges from competition of nonequilibrium active loop extrusion and epigenetically defined compartment structure.

Proliferation-dependent positioning of individual centromeres in the interphase nucleus of human lymphoblastoid cell lines

The cell nucleus is a highly organized structure and plays an important role in gene regulation. Understanding the mechanisms that sustain this organization is therefore essential for understanding genome function. Centromeric regions (CRs) of chromosomes have been known for years to adopt specific nuclear positioning patterns, but the significance of this observation is not yet completely understood. Here, using a combination of fluorescence in situ hybridization and immunochemistry on fixed human cells and high-throughput imaging, we directly and quantitatively investigated the nuclear positioning of specific human CRs. We observe differential attraction of individual CRs toward both the nuclear border and the nucleoli, the former being enhanced in nonproliferating cells and the latter being enhanced in proliferating cells. Similar positioning patterns are observed in two different lymphoblastoid cell lines. Moreover, the positioning of CRs differs from that of noncentromeric regions, and CRs display specific orientations within chromosome territories. These results suggest the existence of not-yet-characterized mechanisms that drive the nuclear positioning of CRs and therefore pave the way toward a better understanding of how CRs affect nuclear organization.