ALBERT

Description: Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2–6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2–6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2–6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2 . Cumulatively, we identified UBE2T as a bona fide FA gene ( FANCT ) that also may be a rare cancer susceptibility gene.

Description: By performing a linear stability analysis in the presence of an external tidal field, we have obtained a generalized dispersion relation for the Parker–Jeans instability. We have found that a compressive tidal field helps in initiating the collapse of the interstellar cloud towards star formation. This effect is present even when the Jeans mass is more than the mass of the system under consideration. In such cases, of course, it is the magnetic field that makes the compressive tidal force effective via the Parker instability. We argue that this effect can be of importance in overcoming the disrupting effect of a random magnetic field.

Description: Deciphering the evolution of the internal dynamics of magmatic plumbing systems and identifying the key parameters that drive such dynamics are major goals of modern volcanology. Here we present a novel petrological approach that combines kinetic modelling of the diffusive relaxation of chemical zoning patterns in olivine crystals with thermodynamic modelling (MELTS) to constrain the nature and evolution of the plumbing system of Mt. Etna and the processes governing its internal dynamics. We investigated the compositional and temporal record preserved in 180 olivine crystals that were erupted between 1991 and 2008. Detailed systemization of the information stored in the sequential zoning record of the olivines reveals the existence of at least five compositionally different magmatic environments (MEs), characterized by different olivine compositions: M 0 (Fo79–83), M 1 (Fo75–78), M 2 (Fo70–72), M 3 (Fo65–69) and mm 1 (Fo73–75). Several routes of magma transfer connect these environments. We identified three prominent magma passageways between the environments M 0 :M 1 , M 2 :mm 1 and M 1 :M 2 that were active during the entire period of observation between 1991 and 2008. Modelling the diffusive relaxation of the olivine zoning patterns reveals that the transfer of magma along such routes can occur over fairly heterogeneous timescales ranging from days to 2 years. Although some of the passageways have been sporadically active in the months and sometimes years before an eruption, the magma migration activity increases clearly in the weeks and days prior to an eruptive event. In this context, major transfer routes such as M 2 :mm 1 might represent temporary passageways that are activated only shortly before eruptive events. A forward modelling approach was developed using thermodynamic calculations with the MELTS software to identify the key intensive variables associated with the different magmatic environments. In this approach the observed populations of mineral compositions (e.g. Fo79–83), rather than single compositions, are associated with thermodynamic parameters [pressure, temperature, water content, oxygen fugacity ( f O 2 ) and bulk composition of the melt] to identify the most plausible set corresponding to each ME. We found that temperature, water content and possibly oxidation state are the main distinguishing features of the different magmatic environments. The most primitive olivine population M 0 (Fo79–83) and some of its associated clinopyroxenes formed at high melt water contents (3·5–5·2 wt %), at f O 2 conditions buffered at quartz–fayalite–magnetite (QFM) or Ni–NiO (NNO), at temperatures ≥1110°C and at pressures ranging between 1·5 and 3·0 kbar (or higher). The intermediate population M 1 (Fo75–78) can be produced over a broad spectrum of conditions, but all require similar temperatures and lower water contents (0·1–1·4 wt %). The most evolved, more Fe-rich olivines of M 2 and M 3 are products of melts with much lower water contants (0·2–1·1 wt % H 2 O for M 2 , 〈0·5 wt % H 2 O for M 3 ), and at probably somewhat more reducing (QFM) conditions at somewhat lower temperatures (~1080°C). The M 3 environment characterized by very low water contents and reducing conditions could be related to an enhanced flux of CO 2 . Combination of the characteristics of the various magmatic environments with temporal information (residence time in different environments and timing of magma transfer between these environments) allows a dynamic model of the plumbing system beneath Mt. Etna to be constructed.

Description: Conifer bark beetles are often associated with fungal complexes whose components have different ecological roles. Some associated species are nutritionally obligate fungi, serving as nourishment to the larvae, whereas others are pathogenic blue-stain fungi known to be involved in the interaction with host defenses. In this study we characterized the local and systemic defense responses of Scots pine ( Pinus sylvestris L.) against Ophiostoma brunneo-ciliatum Math. (a blue-stain pathogen) and Hyalorhinocladiella macrospora (Franke-Grosm.) Harr. (a nutritional fungus). These fungi are the principal associates of the pine engraver beetle, Ips acuminatus (Gyll.). Host responses were studied following inoculation with the fungi, singly and as a fungal complex, and by identifying and quantifying terpenoids, phenolic compounds and lignin. Although the length of the necrotic lesions differed between control (wound) and fungal treatments, only two compounds (pinosylvin monomethyl ether and (+)-α-pinene) were significantly affected by the presence of the fungi, indicating that Scots pine has a generic, rather than specific, induced response. The fact that both nutritional and blue-stain fungi triggered comparable induced defense responses suggests that even a non-pathogenic fungus may participate in exhausting host plant defenses, indirectly assisting in the beetle establishment process. Our findings contribute to the further development of current theory on the role of associated fungal complexes in bark beetle ecology.

Description: Motivation: In a typical gene expression profiling study, our prime objective is to identify the genes that are differentially expressed between the samples from two different tissue types. Commonly, standard analysis of variance (ANOVA)/regression is implemented to identify the relative effects of these genes over the two types of samples from their respective arrays of expression levels. But, this technique becomes fundamentally flawed when there are unaccounted sources of variability in these arrays (latent variables attributable to different biological, environmental or other factors relevant in the context). These factors distort the true picture of differential gene expression between the two tissue types and introduce spurious signals of expression heterogeneity. As a result, many genes which are actually differentially expressed are not detected, whereas many others are falsely identified as positives. Moreover, these distortions can be different for different genes. Thus, it is also not possible to get rid of these variations by simple array normalizations. This both-way error can lead to a serious loss in sensitivity and specificity, thereby causing a severe inefficiency in the underlying multiple testing problem. In this work, we attempt to identify the hidden effects of the underlying latent factors in a gene expression profiling study by partial least squares (PLS) and apply ANCOVA technique with the PLS-identified signatures of these hidden effects as covariates, in order to identify the genes that are truly differentially expressed between the two concerned tissue types. Results: We compare the performance of our method SVA-PLS with standard ANOVA and a relatively recent technique of surrogate variable analysis (SVA), on a wide variety of simulation settings (incorporating different effects of the hidden variable, under situations with varying signal intensities and gene groupings). In all settings, our method yields the highest sensitivity while maintaining relatively reasonable values for the specificity, false discovery rate and false non-discovery rate. Application of our method to gene expression profiling for acute megakaryoblastic leukemia shows that our method detects an additional six genes, that are missed by both the standard ANOVA method as well as SVA, but may be relevant to this disease, as can be seen from mining the existing literature. Availability: The R code for our method, SVA-PLS, is freely available on the Supplementary website http://www.somnathdatta.org/Supp/SVPLS/ Contact: s0chak10@louisville.edu ; susmita.datta@louisville.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: We have performed systematic local linear stability analysis on a radially stratified infinite self-gravitating cylinder of rotating plasma under the influence of magnetic field. In order to render the system analytically tractable, we have focused solely on the axisymmetric modes of perturbations. Using cylindrical coordinate system, we have derived the critical linear mass density of a non-rotating filament required for gravitational collapse to ensue in the presence of azimuthal magnetic field. Moreover, for such filaments threaded by axial magnetic field, we show that the growth rates of the modes having non-zero radial wavenumber are reduced more strongly by the magnetic field than that of the modes having zero radial wavenumber. More importantly, our study contributes to the understanding of the stability property of rotating astrophysical filaments that are more often than not influenced by magnetic fields. In addition to complementing many relevant numerical studies reported the literature, our results on filaments under the influence of magnetic field generalize some of the very recent analytical works. For example, here we prove that even a weak magnetic field can play a dominant role in determining stability of the filament when the rotation time-scale is larger than the free-fall time-scale. A filamentary structure with faster rotation is, however, comparatively more stable for the same magnetic field. The results reported herein, due to strong locality assumption, are strictly valid for the modes for which one can ignore the radial variations in the density and the magnetic field profiles.

Description: In general, proteins do not work alone; they form macromolecular complexes to play fundamental roles in diverse cellular functions. On the basis of their iterative clustering procedure and frequency of occurrence in the macromolecular complexes, the protein subunits have been categorized as core and attachment. Core protein subunits are the main functional elements, whereas attachment proteins act as modifiers or activators in protein complexes. In this article, using the current data set of yeast protein complexes, we found that core proteins are evolving at a faster rate than attachment proteins in spite of their functional importance. Interestingly, our investigation revealed that attachment proteins are present in a higher number of macromolecular complexes than core proteins. We also observed that the protein complex number (defined as the number of protein complexes in which a protein subunit belongs) has a stronger influence on gene/protein essentiality than multifunctionality. Finally, our results suggest that the observed differences in the rates of protein evolution between core and attachment proteins are due to differences in protein complex number and expression level. Moreover, we conclude that proteins which are present in higher numbers of macromolecular complexes enhance their overall expression level by increasing their transcription rate as well as translation rate, and thus the protein complex number imposes a strong selection pressure on the evolution of yeast proteome.

Description: The paper deals with a theoretical model for interacting dark energy (DE). The interaction between the cold dark matter (dust) and the DE has been assumed to be non-gravitational in nature. Exact analytic cosmological solutions are obtained both for constant and variable EoS for DE. It is found that, for very small value of the coupling parameter (in the interaction term), the model asymptotically extends up to cold dark matter, while the model can enter into the phantom domain asymptotically, if the coupling parameter is not so small. Both the solutions are then analysed with 194 Supernovae Type Ia data. The best-fitting parameters are shown with 1 and 2 confidence intervals. Finally, we have discussed the cosmographic parameters for both the cases.