A 3-D in vitro co-culture model of mammary gland involution.

Involution is a process whereby the mammary gland undergoes extensive tissue remodelling involving exquisitely coordinated cell death, extracellular matrix degradation and adipose tissue regeneration following the weaning of offspring. These processes are mediated in part through Jak/Stat signalling pathways, which can be deregulated in breast cancer. Synthetic in vitro analogues of the breast could become important tools for studying tumorigenic processes, or as personalized drug discovery platforms and predictors of therapeutic response. Ideally, such models should support 3D neo-tissue formation, so as to recapitulate physiological organ function, and be compatible with high-throughput screening methodologies. We have combined cell lines of epithelial, stromal and immunological origin within engineered porous collagen/hyaluronic acid matrices, demonstrating 3D-specific molecular signatures. Furthermore seeded cells form mammary-like branched tissues, with lobuloalveolar structures that undergo inducible involution phenotypes reminiscent of the native gland under hormonal/cytokine regulation. We confirm that autophagy is mediated within differentiated mammary epithelial cells in a Stat-dependent manner at early time points following the removal of a prolactin stimulus (H/WD). In addition, epithelial cells express markers of an M2 macrophage lineage under H/WD, a process that is attenuated with the introduction of the monocyte/macrophage cell line RAW 264.7. Thus, such 3D models are suitable platforms for studying cell-cell interactions and cell death mechanisms in relation to cancer.This is the accepted manuscript. The final version is available from RSC at http://pubs.rsc.org/en/content/articlehtml/2014/ib/c3ib40257f

Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development

Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major histocompatibility complex class II molecule expressed in B cells, has previously been shown to be a negative regulator of HLA-DM peptide loading function. We analyze the expression of DO in human peripheral blood, lymph node, tonsil, and bone marrow to determine if DO expression is modulated in the physiological setting. B cells, but not monocytes or monocyte-derived dendritic cells, are observed to express this protein. Preclearing experiments demonstrate that ∼50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM and HLA-DR expression is demonstrated early in B cell development, beginning at the pro-B stage in adult human bone marrow. In contrast, DO expression is initiated only after B cell development is complete. In all situations, there is a striking correlation between intracellular DO expression and cell surface class II–associated invariant chain peptide expression, which suggests that DO substantially inhibits DM function in primary human B cells. We report that the expression of DO is markedly downmodulated in human germinal center B cells. Modulation of DO expression may provide a mechanism to regulate peptide loading activity and antigen presentation by B cells during the development of humoral immune responses

Phase Space Analysis of Quintessence Cosmologies with a Double Exponential Potential

We use phase space methods to investigate closed, flat, and open Friedmann-Robertson-Walker cosmologies with a scalar potential given by the sum of two exponential terms. The form of the potential is motivated by the dimensional reduction of M-theory with non-trivial four-form flux on a maximally symmetric internal space. To describe the asymptotic features of run-away solutions we introduce the concept of a `quasi fixed point.' We give the complete classification of solutions according to their late-time behavior (accelerating, decelerating, crunch) and the number of periods of accelerated expansion.Comment: 46 pages, 5 figures; v2: minor changes, references added; v3: title changed, refined classification of solutions, 3 references added, version which appeared in JCA

Antibacterial Activity of Phenolic Compounds Against the Phytopathogen Xylella fastidiosa

Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties. The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated using an in vitro agar dilution assay. Overall, these phenolic compounds were effective in inhibiting X. fastidiosa growth, as indicated by low minimum inhibitory concentrations (MICs). In addition, phenolic compounds with different structural features exhibited different anti-Xylella capacities. Particularly, catechol, caffeic acid and resveratrol showed strong anti-Xylella activities. Differential response to phenolic compounds was observed among X. fastidiosa strains isolated from grape and almond. Elucidation of secondary metabolite-based host resistance to X. fastidiosa will have broad implication in combating X. fastidiosa-caused plant diseases. It will facilitate future production of plants with improved disease resistance properties through genetic engineering or traditional breeding approaches and will significantly improve crop yield

G = MAT: Linking Transcription Factor Expression and DNA Binding Data

Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/

User-made immobilities: a transitions perspective

In this paper we aim to conceptualize the role of users in creating, expanding and stabilizing the automobility system. Drawing on transition studies we offer a typology of user roles including user-producers, user-legitimators, user-intermediaries, user-citizens and user-consumers, and explore it on the historical transition to the automobile regime in the USA. We find that users play an important role during the entire transition process, but some roles are more salient than others in particular phases. Another finding is that the success of the transition depends on the stabilization of the emerging regime that will trigger upscaling in terms of the numbers of adopters. The findings are used to reflect on potential crossovers between transitions and mobilities research

TOPz: Photometric redshifts for J-PAS

The importance of photometric galaxy redshift estimation is rapidly increasing with the development of specialised powerful observational facilities. We develop a new photometric redshift estimation workflow TOPz to provide reliable and efficient redshift estimations for the upcoming large-scale survey J-PAS which will observe 8500 deg2 of the northern sky through 54 narrow-band filters. TOPz relies on template-based photo-z estimation with some added J-PAS specific features and possibilities. We present TOPz performance on data from the miniJPAS survey, a precursor to the J-PAS survey with an identical filter system. First, we generated spectral templates based on the miniJPAS sources using the synthetic galaxy spectrum generation software CIGALE. Then we applied corrections to the input photometry by minimising systematic offsets from the template flux in each filter. To assess the accuracy of the redshift estimation, we used spectroscopic redshifts from the DEEP2, DEEP3, and SDSS surveys, available for 1989 miniJPAS galaxies with r < 22 magAB. We also tested how the choice and number of input templates, photo-z priors, and photometric corrections affect the TOPz redshift accuracy. The general performance of the combination of miniJPAS data and the TOPz workflow fulfills the expectations for J-PAS redshift accuracy. Similarly to previous estimates, we find that 38.6% of galaxies with r < 22 mag reach the J-PAS redshift accuracy goal of dz/(1 + z) < 0.003. Limiting the number of spectra in the template set improves the redshift accuracy up to 5%, especially for fainter, noise-dominated sources. Further improvements will be possible once the actual J-PAS data become available.Comment: 20 pages, 24 figure

Review of the cultivation program within the National Alliance for Advanced Biofuels and Bioproducts

The cultivation efforts within the National Alliance for Advanced Biofuels and Bioproducts (NAABB)were developed to provide four major goals for the consortium, which included biomass production for downstream experimentation, development of new assessment tools for cultivation, development of new cultivation reactor technologies, and development of methods for robust cultivation. The NAABB consortium test beds produced over 1500 kg of biomass for downstream processing. The biomass production included a number of model production strains, but also took into production some of the more promising strains found through the prospecting efforts of the consortium. Cultivation efforts at large scale are intensive and costly, therefore the consortium developed tools and models to assess the productivity of strains under various environmental conditions, at lab scale, and validated these against scaled outdoor production systems. Two new pond-based bioreactor designs were tested for their ability to minimize energy consumption while maintaining, and even exceeding, the productivity of algae cultivation compared to traditional systems. Also, molecular markers were developed for quality control and to facilitate detection of bacterial communities associated with cultivated algal species, including the Chlorella spp. pathogen, Vampirovibrio chlorellavorus,which was identified in at least two test site locations in Arizona and New Mexico. Finally, the consortium worked on understanding methods to utilize compromised municipal waste water streams for cultivation. This review provides an overview of the cultivation methods and tools developed by the NAABB consortium to produce algae biomass, in robust low energy systems, for biofuel production