Morphogen-defined patterning of Escherichia coli enabled by an externally tunable band-pass filter

<p>Abstract</p> <p>Background</p> <p>Gradients of morphogens pattern cell fate – a phenomenon that is especially important during development. A simple model system for studying how morphogens pattern cell behavior would overcome difficulties inherent in the study of natural morphogens <it>in vivo</it>. A synthetic biology approach to building such a system is attractive.</p> <p>Results</p> <p>Using an externally-tunable band-pass filter paradigm, we engineered <it>Escherichia coli </it>cells to function as a model system for the study of how multiple morphogens can pattern cell behavior. We demonstrate how our system exhibits behavior such as morphogen crosstalk and how the cells' growth and fluorescence can be patterned in a number of complex patterns. We extend our cell patterning from 2D cultures on the surface of plates to 3D cultures in soft agarose medium.</p> <p>Conclusion</p> <p>Our system offers a convenient, well-defined model system for fundamental studies on how multiple morphogen gradients can affect cell fate and lead to pattern formation. Our design principles could be applied to eukaryotic cells to develop other models systems for studying development or for enabling the patterning of cells for applications such as tissue engineering and biomaterials.</p

In Vitro Recombination of Non-Homologous Genes Can Result in Gene Fusions that Confer a Switching Phenotype to Cells

Regulation of protein activity is central to the complexity of life. The ability to regulate protein activity through exogenously added molecules has biotechnological/biomedical applications and offers tools for basic science. Such regulation can be achieved by establishing a means to modulate the specific activity of the protein (i.e. allostery). An alternative strategy for intracellular regulation of protein activity is to control the amount of protein through effects on its production, accumulation, and degradation. We have previously demonstrated that the non-homologous recombination of the genes encoding maltose binding protein (MBP) and TEM1 β-lactamase (BLA) can result in fusion proteins in which β-lactamase enzyme activity is allosterically regulated by maltose. Here, through use of a two-tiered genetic selection scheme, we demonstrate that such recombination can result in genes that confer maltose-dependent resistance to β-lactam even though they do not encode allosteric enzymes. These ‘phenotypic switch’ genes encode fusion proteins whose accumulation is a result of a specific interaction with maltose. Phenotypic switches represent an important class of proteins for basic science and biotechnological applications in vivo

On mixed boundary-value problems for axially-symmetric potentials,

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32440/1/0000522.pd

Integral representations of axially symmetric potential functions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46165/1/205_2004_Article_BF01262704.pd

On the scattering of waves by a disk

Es wird gezeigt, dass das Problem, die Beugung einer ebenen Welle an einer kreisförmigen Öffnung oder Scheibe zu bestimmen, auf die Lösung von regulären Fredholmschen Integralgleichungen zweiter Art zurückgeführt werden kann. Die Lösungen dieser Integralgleichungen liefern uns für die Scheibe im Falle der Neumannschen Bedingung die radiale Variation der Unstetigkeiten der Wellenfunktion und im Dirichletschen Falle die Unstetigkeiten ihrer normalen Ableitung. Ist das Produkt von Öffnungsradius und Wellenzahl klein, so können die Integralgleichungen gelöst werden. Für die Ableitung der Integralgleichungen verwenden wir einerseits die Poissonsche Darstellung für die Wellenfunktion und andererseits die Fortsetzung der Helmholtzschen Darstellung in die komplexe Ebene.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43290/1/33_2005_Article_BF01602674.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

A pilot validation of a modified Illness Perceptions Questionnaire designed to predict response to cognitive therapy for psychosis

Background and objectives: Clinical responsiveness to cognitive behavioural therapy for psychosis (CBTp) varies. Recent research has demonstrated that illness perceptions predict active engagement in therapy, and, thereby, better outcomes. In this study, we aimed to investigate the psychometric properties of a modification of the Illness Perceptions Questionnaire (M-IPQ) designed to predict response following CBTp. Methods: Fifty-six participants with persistent, distressing delusions completed the M-IPQ; forty before a brief CBT intervention targeting persecutory ideation and sixteen before and after a control condition. Additional predictors of outcome (delusional conviction, symptom severity and belief inflexibility) were assessed at baseline. Outcomes were assessed at baseline and at follow-up four to eight weeks later. Results: The M-IPQ comprised two factors measuring problem duration and therapy-specific perceptions of Cure/Control. Associated subscales, formed by summing the relevant items for each factor, were reliable in their structure. The Cure/Control subscale was also reliable over time; showed convergent validity with other predictors of outcome; predicted therapy outcomes; and differentially predicted treatment effects. Limitations: We measured outcome without an associated measure of engagement, in a small sample. Findings are consistent with hypothesis and existing research, but require replication in a larger, purposively recruited sample. Conclusions: The Cure/Control subscale of the M-IPQ shows promise as a predictor of response to therapy. Specifically targeting these illness perceptions in the early stages of cognitive behavioural therapy may improve engagement and, consequently, outcomes