myGRN: a database and visualisation system for the storage and analysis of developmental genetic regulatory networks

<p>Abstract</p> <p>Background</p> <p>Biological processes are regulated by complex interactions between transcription factors and signalling molecules, collectively described as Genetic Regulatory Networks (GRNs). The characterisation of these networks to reveal regulatory mechanisms is a long-term goal of many laboratories. However compiling, visualising and interacting with such networks is non-trivial. Current tools and databases typically focus on GRNs within simple, single celled organisms. However, data is available within the literature describing regulatory interactions in multi-cellular organisms, although not in any systematic form. This is particularly true within the field of developmental biology, where regulatory interactions should also be tagged with information about the time and anatomical location of development in which they occur.</p> <p>Description</p> <p>We have developed myGRN (<url>http://www.myGRN.org</url>), a web application for storing and interrogating interaction data, with an emphasis on developmental processes. Users can submit interaction and gene expression data, either curated from published sources or derived from their own unpublished data. All interactions associated with publications are publicly visible, and unpublished interactions can only be shared between collaborating labs prior to publication. Users can group interactions into discrete networks based on specific biological processes. Various filters allow dynamic production of network diagrams based on a range of information including tissue location, developmental stage or basic topology. Individual networks can be viewed using myGRV, a tool focused on displaying developmental networks, or exported in a range of formats compatible with third party tools. Networks can also be analysed for the presence of common network motifs. We demonstrate the capabilities of myGRN using a network of zebrafish interactions integrated with expression data from the zebrafish database, ZFIN.</p> <p>Conclusion</p> <p>Here we are launching myGRN as a community-based repository for interaction networks, with a specific focus on developmental networks. We plan to extend its functionality, as well as use it to study networks involved in embryonic development in the future.</p

Cloning and characterization of novel methylsalicylic acid synthase gene involved in the biosynthesis of isoasperlactone and asperlactone in Aspergillus westerdijkiae

Aspergillus westerdijkiae is the main producer of several biologically active polyketide metabolites including isoasperlactone and asperlactone. A 5298 bp polyketide synthase gene ‘‘aomsas” has been cloned in Aspergillus westerdijkiae by using gene walking approach and RACE-PCR. The predicted amino acid sequence of aomsas shows an identity of 40–56% with different methylsalicylic acid synthase genes found in Byssochlamys nivea, P. patulum, A. terreus and Streptomyces viridochromogenes. Based on the reverse transcription PCR and kinetic secondary metabolites production studies, aomsas expression was found to be associated with the biosynthesis of isoasperlactone and asperlactone. Moreover an aomsas knockout mutant ‘‘aoDmsas” of A. westerdijkiae, not only lost the capacity to produce isoasperlactone and asperlactone,but also 6-methylsalicylic acid. The genetically complemented mutant ao+msas restored the biosynthesis of all the missing metabolites. Chemical complementation through the addition of 6-methylsalicylic acid, aspyrone and diepoxide to growing culture of aoDmsas mutant revealed that these compounds play intermediate roles in the biosynthesis of asperlactone and isoasperlactone

Green Propellant Landing Demonstration at U.S. Range

The Green Propellant Loading Demonstration (GPLD) was conducted December 2015 at Wallops Flight Facility (WFF), leveraging work performed over recent years to bring lower toxicity hydrazine replacement green propellants to flight missions. The objective of this collaboration between NASA Goddard Space Flight Center (GSFC), WFF, the Swedish National Space Board (SNSB), and Ecological Advanced Propulsion Systems (ECAPS) was to successfully accept LMP-103S propellant at a U.S. Range, store the propellant, and perform a simulated flight vehicle propellant loading. NASA GSFC Propulsion (Code 597) managed all aspects of the operation, handling logistics, preparing the procedures, and implementing the demonstration. In addition to the partnership described above, Moog Inc. developed an LMP-103S propellant-compatible titanium rolling diaphragm flight development tank and loaned it to GSFC to act as the GPLD flight vessel. The flight development tank offered the GPLD an additional level of flight-like propellant handling process and procedures. Moog Inc. also provided a compatible latching isolation valve for remote propellant expulsion. The GPLD operation, in concert with Moog Inc. executed a flight development tank expulsion efficiency performance test using LMP-103S propellant. As part of the demonstration work, GSFC and WFF documented Range safety analyses and practices including all elements of shipping, storage, handling, operations, decontamination, and disposal. LMP-103S has not been previously handled at a U.S. Launch Range. Requisite for this activity was an LMP-103S Risk Analysis Report and Ground Safety Plan. GSFC and WFF safety offices jointly developed safety documentation for application into the GPLD operation. The GPLD along with the GSFC Propulsion historical hydrazine loading experiences offer direct comparison between handling green propellant versus safety intensive, highly toxic hydrazine propellant. These described motives initiated the GPLD operation in order to investigate the handling and process safety variances in project resources between LMP-103S and typical in-space propellants. The GPLD risk reduction operation proved successful for many reasons including handling the green propellant at a U.S. Range, loading and pressurizing a flight-like tank, expelling the propellant, measuring the tank expulsion efficiency, and most significantly, GSFC propulsion personnel's new insight into the LMP-103S propellant handling details

Hydrophilic modification of SLA 3D printed droplet generators by photochemical grafting

Few droplet generators manufactured using desktop stereolithography 3D printers have been reported in the literature. Moreover, 3D printed microfluidic chips are typically hydrophobic, limiting their application to water in oil droplets. Herein, we present designs for concentric and planar 3D printed microfluidic devices suitable for making polymeric microparticles using an off-the-shelf commercial stereolithography printer and resin. The devices consist of a microscope slide, binder clips, and printed components. Channels were modified by an ultraviolet grafting of methacrylic acid to the surface of chips, yielding a hydrophilic coating without modification to the bulk polymer. The water contact angle decreased from 97.0° to 25.4° after grafting. The presence of the coating was confirmed by microscopy and spectroscopy techniques. Polystyrene microparticles in the \u3c100 μm size range were generated with varying molecular weights using the described microfluidic chips. Our work provides a facile method to construct droplet generators from commercial stereolithography printers and resins, and a rapid surface modification technique that has been under-utilized in 3D printed microfluidics. A wide range of microfluidic devices for other applications can be engineered using the methods described

Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134500/1/pedi12340.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134500/2/pedi12340_am.pd

A cross‐sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136377/1/pedi12377_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136377/2/pedi12377.pd

Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

Lattice statistical mechanics, often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in a general mathematical framework, be too complex, or could not be defined. Considering several Picard-Fuchs systems of two-variables "above" Calabi-Yau ODEs, associated with double hypergeometric series, we show that holonomic functions are actually a good framework for actually finding the singular manifolds. We, then, analyse the singular algebraic varieties of the n-fold integrals $\chi^{(n)}$, corresponding to the decomposition of the magnetic susceptibility of the anisotropic square Ising model. We revisit a set of Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find a first set of non-Nickelian singularities for $\chi^{(3)}$ and $\chi^{(4)}$, that also turns out to be rational or ellipic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model. We address, from a birational viewpoint, the emergence of families of elliptic curves, and of Calabi-Yau manifolds on such problems. We discuss the accumulation of these singular curves for the non-holonomic anisotropic full susceptibility.Comment: 36 page

Survival and Clinical Course at Fontan After Stage One Palliation With Either a Modified Blalock-Taussig Shunt or a Right Ventricle to Pulmonary Artery Conduit

ObjectivesWe sought to determine whether the type of shunt used at stage one palliation (S1P) affected the survival and the perioperative course through Fontan completion.BackgroundAlthough improved surgical and interstage survival have been demonstrated with the use of the right ventricle to pulmonary artery (RV-PA) conduit compared with a modified Blalock-Taussig shunt (BTS) at S1P, it is unknown whether this effect will be observed in long-term follow-up.MethodsAll patients who underwent a S1P during 2002 and 2003 (n = 80) at our institution were included for analysis. Patients were followed until death or June 1, 2007. Perioperative variables at Fontan completion were recorded.ResultsFor the entire cohort, cumulative survival for those who underwent a RV-PA conduit (n = 34) was 79.4% at 3 years compared with 65.8% in the modified BTS group (n = 46) (log-rank = 0.31). At Fontan (n = 44), when compared with those who had received a modified BTS, those who had a RV-PA conduit placed at S1P had no difference in the median duration of ventilation (21 h [range 10 to 96 h] vs. 26.5 h [range 7 to 204 h], p = 0.09) or hospital stay (9 days [range 5 to 29 days] vs. 10 days [range 6 to 48 days], p = 0.89), although length of stay in the intensive care unit was shorter (2 days [range 0 to 6 days] vs. 4 days [range 1 to 25 days], p = 0.01). Sixty-seven percent of the RV-PA conduit group had at least one PA intervention 3 years after S1P compared with 42.8% in the modified BTS group (log-rank = 0.11).ConclusionsNonstatistically significant trends toward improved cumulative survival and increased PA interventions were demonstrated in patients who had a RV-PA conduit placed at S1P. Longitudinal follow-up of larger groups of randomized patients is required to determine the influence of the RV-PA conduit on long-term outcomes

Ergosterol Effect on the Desaturation of 14C-Cis-Vaccenate in Tetrahymena

Supplement of ergosterol to the growth medium of the ciliated protozoan Tetrahymena pyriformis W leads to incorporation of the foreign sterol within cell membranes and suppression of synthesis of the native sterol-like compound tetrahymanol, as well as to changes in the fatty acid compositions of several major classes of membrane lipid. Alteration of fatty acid composition is thought to represent a regulatory mechanism whereby optimum membrane fluidity is maintained when the slightly dissimilar foreign sterol is added into the phospholipid bilayer of the membranes. The present study, using several different conditions of growth temperature, substrate concentrations and incubation time, and ergosterol concentrations and exposure time, is an attempt to provide evidence supporting a hypothetical regulatory mechanism. This mechanism proposes that there is a feedback regulation by membrane-bound sterol on an enzyme or enzymes involved in synthesis of the long chain fatty acids contained in membrane phospholipid. Such a mechanism could account for the balance between sterol and fatty acid content of membrane. The data presented here show that a statistically significant increase in desaturation of 14C-cis-vaccenate can be demonstrated in Tetrahymena cell cultures whose membranes contain the foreign sterol, when growth temperature is maintained at 20° or 29.5°. Tetrahymena desaturated 14C-cis-vaccenate substrate in both ergosterol supplemented and normal cultures. The 14C labeled product, 6,11-18:2 was recovered and separated by silver nitrate-Unisil column chromatography