Direct Identification of the Meloidogyne incognita Secretome Reveals Proteins with Host Cell Reprogramming Potential

The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin) that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins). Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth). Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodeling. Recently microglial cells have been shown to be responsible for a portion of synaptic remodeling, but the remaining mechanisms remain mysterious. Here we report a new role for astrocytes in actively engulfing CNS synapses. This process helps to mediate synapse elimination, requires the Megf10 and Mertk phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to normally refine their retinogeniculate connections and retain excess functional synapses. Lastly, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify Megf10 and Mertk as critical players in the synapse remodeling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes

Lack of Evidence for Neonatal Misoprostol Neurodevelopmental Toxicity in C57BL6/J Mice

Misoprostol is a synthetic analogue of prostaglandin E1 that is administered to women at high doses to induce uterine contractions for early pregnancy termination and at low doses to aid in cervical priming during labor. Because of the known teratogenic effects of misoprostol when given during gestation and its effects on axonal growth in vitro, we examined misoprostol for its potential as a neurodevelopmental toxicant when administered to neonatal C57BL6/J mice. Mice were injected subcutaneously (s.c.) with 0.4, 4 or 40 µg/kg misoprostol on postnatal day 7, the approximate developmental stage in mice of human birth, after which neonatal somatic growth, and sensory and motor system development were assessed. These doses were selected to span the range of human exposure used to induce labor. In addition, adult mice underwent a battery of behavioral tests relevant to neurodevelopmental disorders such as autism including tests for anxiety, stereotyped behaviors, social communication and interactions, and learning and memory. No significant effects of exposure were found for any measure of development or behavioral endpoints. In conclusion, the results of the present study in C57BL/6J mice do not provide support for neurodevelopmental toxicity after misoprostol administration approximating human doses and timed to coincide with the developmental stage of human birth

Structural magnetic glassiness in the spin ice Dy2 Ti2 O7

The origin and nature of glassy dynamics presents one of the central enigmas of condensed-matter physics across a broad range of systems ranging from window glass to spin glasses. The spin-ice compound Dy2Ti2O7, which is perhaps best known as hosting a three-dimensional Coulomb spin liquid with magnetically charged monopole excitations, also falls out of equilibrium at low temperature. How and why it does so remains an open question. Based on an analysis of low-temperature diffuse neutron-scattering experiments employing different cooling protocols alongside recent magnetic noise studies, combined with extensive numerical modeling, we argue that upon cooling, the spins freeze into what may be termed a "structural magnetic glass,"without an a priori need for chemical or structural disorder. Specifically, our model indicates the presence of frustration on two levels, first producing a near-degenerate constrained manifold inside which phase ordering kinetics is in turn frustrated. A remarkable feature is that monopoles act as sole annealers of the spin network and their pathways and history encode the development of glass dynamics, allowing the glass formation to be visualized. Our results suggest that spin ice Dy2Ti2O7 provides one prototype of magnetic glass formation specifically and a setting for the study of kinetically constrained systems more generally