Utilizing Gene Tree Variation to Identify Candidate Effector Genes in Zymoseptoria tritici

Zymoseptoria tritici is a host-specific, necrotrophic pathogen of wheat. Infection by Z. tritici is characterized by its extended latent period, which typically lasts two weeks, and is followed by extensive host cell death and rapid proliferation of fungal biomass. This work characterizes the level of genomic variation in 13 isolates for which we have measured virulence on 11 wheat cultivars with differential resistance genes. Between the reference isolate, IPO323, and the 13 Australian isolates we identified over 800,000 single nucleotide polymorphisms, of which ~10% had an effect on the coding regions of the genome. Furthermore we identified over 1700 probable presence/absence polymorphisms in genes across the Australian isolates using de novo assembly. Finally, we developed a gene tree sorting method that quickly identifies groups of isolates within a single gene alignment whose sequence haplotypes correspond with virulence scores on a single wheat cultivar. Using this method we have identified <100 candidate effector genes whose gene sequence correlates with virulence towards a wheat cultivar carrying a major resistance gene

Deep Neural Networks Rival the Representation of Primate IT Cortex for Core Visual Object Recognition

The primate visual system achieves remarkable visual object recognition performance even in brief presentations and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition). This remarkable performance is mediated by the representation formed in inferior temporal (IT) cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs). It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations such as the amount of noise, the number of neural recording sites, and the number trials, and computational limitations such as the complexity of the decoding classifier and the number of classifier training examples. In this work we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of "kernel analysis" that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.Comment: 35 pages, 12 figures, extends and expands upon arXiv:1301.353

Well-differentiated papillary mesothelioma of the peritoneum is genetically defined by mutually exclusive mutations in TRAF7 and CDC42.

Well-differentiated papillary mesothelioma is an uncommon mesothelial neoplasm that most frequently arises in the peritoneal cavity of women of reproductive age. Whereas malignant mesothelioma is an aggressive tumor associated with poor outcome, well-differentiated papillary mesothelioma typically exhibits indolent behavior. However, histologically differentiating between these two entities can be challenging, necessitating the development of distinguishing biomarkers. While the genetic alterations that drive malignant mesothelioma have recently been determined, the molecular pathogenesis of well-differentiated papillary mesothelioma is unknown. Here we performed genomic profiling on a cohort of ten well-differentiated papillary mesothelioma of the peritoneum. We identified that all tumors harbored somatic missense mutations in either the TRAF7 or CDC42 genes, and lacked alterations involving BAP1, NF2, CDKN2A, DDX3X, SETD2, and ALK that are frequent in malignant mesothelioma. We recently identified that another mesothelial neoplasm, adenomatoid tumor of the genital tract, is genetically defined by somatic missense mutations in the TRAF7 gene, indicating a shared molecular pathogenesis between well-differentiated papillary mesothelioma and adenomatoid tumors. To the best of our knowledge, well-differentiated papillary mesothelioma is the first human tumor type found to harbor recurrent mutations in the CDC42 gene, which encodes a Rho family GTPase. Immunohistochemistry demonstrated intact BAP1 expression in all cases of well-differentiated papillary mesothelioma, indicating that this is a reliable marker for distinguishing well-differentiated papillary mesothelioma from malignant mesotheliomas that frequently display loss of expression. Additionally, all well-differentiated papillary mesothelioma demonstrated robust expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation, similar to that observed in adenomatoid tumors. In contrast, we have previously shown that L1CAM staining is not observed in normal mesothelial cells and malignant mesotheliomas of the peritoneum. Together, these studies demonstrate that well-differentiated papillary mesothelioma is genetically defined by mutually exclusive mutations in TRAF7 and CDC42 that molecularly distinguish this entity from malignant mesothelioma

The impact of omega-3 fatty acid use on the risk of atrial fibrillation in patients with cardiovascular disease

This is an Open Access article distributed under the terms of the Open Access Policy

Chromatin conformation signatures of cellular differentiation

A suite of computer programs to identify genome-wide chromatin conformation signatures with 5C technology is reported

Tomographic Reconstruction of Mercury's Exosphere from MESSENGER Flyby Data

The exosphere of Mercury is among the best-studied examples of a common type of atmosphere, a surface-bounded exosphere. Mercury's exosphere was probed in 2008-2009 with Ultraviolet and Visible Spectrometer (UVVS) measurements obtained during three planetary flybys by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft [1-3]. The measurements detailed the distribution of two previously known metallic constituents of Mercury's exosphere, Na and Ca, and indicated the presence in the gas phase of yet another metallic species, Mg. Such measurements can answer fundamental scientific questions regarding the relative importance of possible source and loss processes for exospheric species ejected from a surface boundary [4]. The trajectory of MESSENGER during the last of its three flybys provided the best spatial coverage prior to orbit insertion. The measurements by MESSENGER of Na, Ca, and Mg during the third flyby have been analyzed with a novel tomographic method. This approach maximizes the amount of information that can be extracted from line-of-sight measurements because it yields three-dimensional distributions of neutrals consistent with the data

Survey of Coherent Approximately 1 Hz Waves in Mercury's Inner Magnetosphere from MESSENGER Observations

We summarize observations by the MESSENGER spacecraft of highly coherent waves at frequencies between 0.4 and 5 Hz in Mercury's inner magnetosphere. This survey covers the time period from 24 March to 25 September 2011, or 2.1 Mercury years. These waves typically exhibit banded harmonic structure that drifts in frequency as the spacecraft traverses the magnetic equator. The waves are seen at all magnetic local times, but their observed rate of occurrence is much less on the dayside, at least in part the result of MESSENGER's orbit. On the nightside, on average, wave power is maximum near the equator and decreases with increasing magnetic latitude, consistent with an equatorial source. When the spacecraft traverses the plasma sheet during its equatorial crossings, wave power is a factor of 2 larger than for equatorial crossings that do not cross the plasma sheet. The waves are highly transverse at large magnetic latitudes but are more compressional near the equator. However, at the equator the transverse component of these waves increases relative to the compressional component as the degree of polarization decreases. Also, there is a substantial minority of events that are transverse at all magnetic latitudes, including the equator. A few of these latter events could be interpreted as ion cyclotron waves. In general, the waves tend to be strongly linear and characterized by values of the ellipticity less than 0.3 and wave-normal angles peaked near 90 deg. Their maxima in wave power at the equator coupled with their narrow-band character suggests that these waves might be generated locally in loss cone plasma characterized by high values of the ratio beta of plasma pressure to magnetic pressure. Presumably both electromagnetic ion cyclotron waves and electromagnetic ion Bernstein waves can be generated by ion loss cone distributions. If proton beta decreases with increasing magnetic latitude along a field line, then electromagnetic ion Bernstein waves are predicted to transition from compressional to transverse, a pattern consistent with our observations. We hypothesize that these local instabilities can lead to enhanced ion precipitation and directly feed field-line resonances

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation.

Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wild-type TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation

The Velocity Distribution of Pickup He+ Measured at 3.0 AU By Messenger

During its interplanetary trajectory in 2007–2009, the MErcury Surface, Space ENvrionment, GEochemistry, and Ranging (MESSENGER) spacecraft passed through the gravitational focusing cone for interstellar helium multiple times at a heliocentric distance R ≈ 0.3 AU. Observations of He+ interstellar pickup ions made by the Fast Imaging Plasma Spectrometer sensor on MESSENGER during these transits provide a glimpse into the structure of newly formed inner heliospheric pickup-ion distributions. This close to the Sun, these ions are picked up in a nearly radial interplanetary magnetic field. Compared with the near-Earth environment, pickup ions observed near 0.3 AU will not have had sufficient time to be energized substantially. Such an environment results in a nearly pristine velocity distribution function that should depend only on pickup-ion injection velocities (related to the interstellar gas), pitch-angle scattering, and cooling processes. From measured energy-per-charge spectra obtained during multiple spacecraft observational geometries, we have deduced the phase-space density of He+ as a function of magnetic pitch angle. Our measurements are most consistent with a distribution that decreases nearly monotonically with increasing pitch angle, rather than the more commonly modeled isotropic or hemispherically symmetric forms. These results imply that pitch-angle scattering of He+ may not be instantaneous, as is often assumed, and instead may reflect the velocity distribution of initially injected particles. In a slow solar wind stream, we find a parallel-scattering mean free path of λ ∼ 0.1 AU and a He+ production rate of ∼0.05 m−3 s−1 within 0.3 AU

Thermal Evolution of Mercury as Constrained by MESSENGER Observations

Orbital observations of Mercury by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft provide new constraints on that planet's thermal and interior evolution. Specifically, MESSENGER observations have constrained the rate of radiogenic heat production via measurement of uranium, thorium, and potassium at the surface, and identified a range of surface compositions consistent with high-temperature, high-degree partial melts of the mantle. Additionally, MESSENGER data have placed new limits on the spatial and temporal variation in volcanic and tectonic activity and enabled determination that the planet's core is larger than previously estimated. Because Mercury's mantle layer is also thinner than previously thought, this result gives greater likelihood to the possibility that mantle convection is marginally supercritical or even that the mantle is not convecting. We simulate mantle convection and magma generation within Mercury's mantle under two-dimensional axisymmetry and a broad range of conditions to understand the implications of MESSENGER observations for the thermal evolution of the planet. These models demonstrate that mantle convection can persist in such a thin mantle for a substantial portion of Mercury's history, and often to the present, as long as the mantle is thicker than ~300 km. We also find that magma generation in Mercury's convecting mantle is capable of producing widespread magmas by large-degree partial melting, consistent with MESSENGER observations of the planet's surface chemistry and geology