SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

<p>Abstract</p> <p>Background</p> <p>It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models.</p> <p>Results</p> <p>This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface.</p> <p>Conclusion</p> <p>SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.</p

Study of the X-ray properties of the neutron-star binary 4U 1728−-34 from the soft to hard state

We studied five XMM-Newton observations of the neutron-star binary 4U 1728$-$34 covering the hard, intermediate and soft spectral states. By jointly fitting the spectra with several reflection models, we obtained an inclination angle of 25$-$53$\deg$ and an iron abundance up to 10 times the solar. From the fits with reflection models, we found that the fluxes of the reflection and the Comptonised components vary inconsistently; since the latter is assumed to be the illuminating source, this result possibly indicates the contribution of the neutron star surface/boundary layer to the disc reflection. As the source evolved from the relatively soft to the intermediate state, the disc inner radius decreased, opposite to the prediction of the standard accretion disc model. We also explore the possible reasons why the supersolar iron abundance is required by the data and found that this high value is probably caused by the absence of the hard photons in the XMM-Newton data.Comment: 14 pages, 6 figure

Result of 2004 extended trypanosomosis survey of ruminants at Kachia Grazing Reserve, North Central Nigeria

Tsetse fly and trypanosome prevalence in ruminants were estimated in April and August, peak months of the dry and rainy seasons in the Kachia Grazing Reserve (KGR) of Kaduna State, North Central Nigeria. This study was subsequent to reports of seasonal outmigration of semi nomadic Fulani from the grazing reserve due to death of cattle from trypanosomosis. Result of blood samples showed an overall parasitological infection rate of 17.4%. Infection rates in cattle, sheep and goats were, 18.6%, 9.5% and 5.1% respectively. Over all higher infection rate in the rainy season was attributed to abundance of tsetse and other hematophagus flies. Infection rate in younger animals (21.9%) was higher compared to those of older animals (16.5%). Trypanosoma vivax was the dominant infecting trypanosome specie followed by T. congolense and T. brucei.It was concluded that tsetse fly and trypanosomosis constituted dual plagues limiting economic livestock production and settling of the pastoralists in the grazing reserve. This warrants application of sustainable integrated control measures to enhance utilization of abundant fodder at the reserve.Key words: Kachia grazing reserve, trypanosomosis, ruminants, infection rates, Nigeria. Resultat de l'enquete de trypanosomose extension de 2004 des ruminants a la reserve de piscine Kachia, Nigeria Centrale du NordLa prévalence de la mouche tsé-tsé et du trypanosome chez les ruminants a été estimée en avril et août, les mois de pointe des saisons secanes et pluvieuses dans la réserve de pâturage de Kachia (KGR) de l'État de Kaduna, dans le nord du centre du Nigeria. Cette étude a été postérieure à des rapports d'émigration saisonnière de Fulani semi-nomades provenant de la réserve de pâturage en raison de la mort de bovins de la trypanosomose. Le résultat des échantillons de sang a montré un taux global d'infection parasitaire de 17,4%. Les taux d'infection chez les bovins, les ovins et les chèvres étaient respectivement de 18,6%, 9,5% et 5,1%. Le taux d'infection plus élevé pendant la saison des pluies a été attribué à l'abondance de mouches tsé-tsé et d'autres mouches hématophobes. Le taux d'infection chez les animaux plus jeunes (21,9%) était plus élevé par rapport à ceux des animaux plus âgés (16,5%). Trypanosoma vivax était le trypanosome infectant dominant suivi de T. congolense et T. brucei.On a conclu que la mouche tsé-tsé et la trypanosomose constituaient des fléaux doubles limitant la production d'élevage économique et la colonisation des pasteurs dans la réserve de pâturage. Cela justifie l'application de mesures de contrôle intégrées durables pour améliorer l'utilisation de fourrages abondants dans la réserve.Mots clés: réserve de pâturage de Kachia, trypanosomose, ruminants, taux d'infection, Nigeri

Autoimmunity conferred by chs3-2D relies on CSA1, its adjacent TIR-NB-LRR encoding neighbour

Plant innate immunity depends on the function of a large number of intracellular immune receptor proteins, the majority of which are structurally similar to mammalian nucleotidebinding oligomerization domain (NOD)-like receptor (NLR) proteins. CHILLING SENSITIVE 3 (CHS3) encodes an atypical Toll/Interleukin 1 Receptor (TIR)-type NLR protein with an additional Lin-11, Isl-1 and Mec-3 (LIM) domain at its C-terminus. The gain-of-function mutant allele chs3-2D exhibits severe dwarfism and constitutively activated defense responses, including enhanced resistance to virulent pathogens, high defence marker gene expression, and salicylic acid accumulation. To search for novel regulators involved in CHS3-mediated immune signaling, we conducted suppressor screens in the chs3-2D and chs3-2D pad4-1 genetic backgrounds. Alleles of sag101 and eds1-90 were isolated as complete suppressors of chs3-2D, and alleles of sgt1b were isolated as partial suppressors of chs3-2D pad4-1. These mutants suggest that SAG101, EDS1-90, and SGT1b are all positive regulators of CHS3-mediated defense signaling. Additionally, the TIR-type NLR-encoding CSA1 locus located genomically adjacent to CHS3 was found to be fully required for chs3-2D-mediated autoimmunity. CSA1 is located 3.9kb upstream of CHS3 and is transcribed in the opposite direction. Altogether, these data illustrate the distinct genetic requirements for CHS3-mediated defense signaling

Zn3As2 Nanowires and nanoplatelets: highly efficient infrared emission and photodetection by an earth abundant material

The development of earth abundant materials for optoelectronics and photovoltaics promises improvements in sustainability and scalability. Recent studies have further demonstrated enhanced material efficiency through the superior light management of novel nanoscale geometries such as the nanowire. Here we show that an industry standard epitaxy technique can be used to fabricate high quality II-V nanowires (1D) and nanoplatelets (2D) of the earth abundant semiconductor Zn3As2. We go on to establish the optoelectronic potential of this material by demonstrating efficient photoemission and detection at 1.0 eV, an energy which is significant to the fields of both photovoltaics and optical telecommunications. Through dynamical spectroscopy this superior performance is found to arise from a low rate of surface recombination combined with a high rate of radiative recombination. These results introduce nanostructured Zn3As2 as a high quality optoelectronic material ready for device exploration.T.B., P.C., Y.G., H.H.T., and C.J. acknowledge the Australian Research Council. T.B., P.C., Y.G., H.H.T., and C.J. thank the Australian National Fabrication Facility for access to the growth and microscopy facilities and Centre for Advanced Microscopy and Australian Microscopy and Microanalysis Research Facility for access to microscopy facilities used in this work. Y.W., B.B., H.E.J., and L.M.S. acknowledge the financial support of the National Science Foundation through grants DMR-1105362, 1105121, and ECCS-1100489

Genetics of Dothistromin Biosynthesis in the Peanut Pathogen Passalora arachidicola

The peanut leaf spot pathogen Passalora arachidicola (Mycosphaerella arachidis) is known to produce dothistromin, a mycotoxin related to aflatoxin. This is a feature shared with the pine needle pathogen Dothistroma septosporum (Mycosphaerella pini). Dothistromin biosynthesis in D. septosporum commences at an unusually early stage of growth in culture compared to most other fungal secondary metabolites, and the biosynthetic genes are arranged in fragmented groups, in contrast to aflatoxin gene clusters. Dothistromin biosynthetic genes were identified and studied in P. arachidicola to determine if the attributes described in D. septosporum are shared by another dothistromin-producing species within the Class Dothideomycetes. It was shown that dothistromin biosynthesis is very similar in the two species with regard to gene sequence and gene synteny. Functional complementation of D. septosporum mutants with P. arachidicola dothistromin genes was also possible. These similarities support a vertical mode of dothistromin gene transmission. P. arachidicola also produced dothistromin at an early growth stage in culture, suggesting that this type of regulation pattern may be relevant to the biological role of dothistromin

Collective magnetism at multiferroic vortex domain walls

Topological defects have been playgrounds for many emergent phenomena in complex matter such as superfluids, liquid crystals, and early universe. Recently, vortex-like topological defects with six interlocked structural antiphase and ferroelectric domains merging into a vortex core were revealed in multiferroic hexagonal manganites. Numerous vortices are found to form an intriguing self-organized network. Thus, it is imperative to find out the magnetic nature of these vortices. Using cryogenic magnetic force microscopy, we discovered unprecedented alternating net moments at domain walls around vortices that can correlate over the entire vortex network in hexagonal ErMnO3 The collective nature of domain wall magnetism originates from the uncompensated Er3+ moments and the correlated organization of the vortex network. Furthermore, our proposed model indicates a fascinating phenomenon of field-controllable spin chirality. Our results demonstrate a new route to achieving magnetoelectric coupling at domain walls in single-phase multiferroics, which may be harnessed for nanoscale multifunctional devices.Comment: 18 pages, 10 figure

Functional analysis of RXLR effectors from the New Zealand kauri dieback pathogen Phytophthora agathidicida

New Zealand kauri is an ancient, iconic, gymnosperm tree species that is under threat from a lethal dieback disease caused by the oomycete Phytophthora agathidicida. To gain insight into this pathogen, we determined whether proteinaceous effectors of P. agathidicida interact with the immune system of a model angiosperm, Nicotiana, as previously shown for Phytophthora pathogens of angiosperms. From the P. agathidicida genome, we defined and analysed a set of RXLR effectors, a class of proteins that typically have important roles in suppressing or activating the plant immune system. RXLRs were screened for their ability to activate or suppress the Nicotiana plant immune system using Agrobacterium tumefaciens transient transformation assays. Nine P. agathidicida RXLRs triggered cell death or suppressed plant immunity in Nicotiana, of which three were expressed in kauri. For the most highly expressed, P. agathidicida (Pa) RXLR24, candidate cognate immune receptors associated with cell death were identified in Nicotiana benthamiana using RNA silencing-based approaches. Our results show that RXLRs of a pathogen of gymnosperms can interact with the immune system of an angiosperm species. This study provides an important foundation for studying the molecular basis of plant–pathogen interactions in gymnosperm forest trees, including kauri

Spermine Synthase and MYC Cooperate to Maintain Colorectal Cancer Cell Survival by Repressing Bim Expression

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing Bim. These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC