RNAstructure: software for RNA secondary structure prediction and analysis

<p>Abstract</p> <p>Background</p> <p>To understand an RNA sequence's mechanism of action, the structure must be known. Furthermore, target RNA structure is an important consideration in the design of small interfering RNAs and antisense DNA oligonucleotides. RNA secondary structure prediction, using thermodynamics, can be used to develop hypotheses about the structure of an RNA sequence.</p> <p>Results</p> <p>RNAstructure is a software package for RNA secondary structure prediction and analysis. It uses thermodynamics and utilizes the most recent set of nearest neighbor parameters from the Turner group. It includes methods for secondary structure prediction (using several algorithms), prediction of base pair probabilities, bimolecular structure prediction, and prediction of a structure common to two sequences. This contribution describes new extensions to the package, including a library of C++ classes for incorporation into other programs, a user-friendly graphical user interface written in JAVA, and new Unix-style text interfaces. The original graphical user interface for Microsoft Windows is still maintained.</p> <p>Conclusion</p> <p>The extensions to RNAstructure serve to make RNA secondary structure prediction user-friendly. The package is available for download from the Mathews lab homepage at <url>http://rna.urmc.rochester.edu/RNAstructure.html</url>.</p

Embodied Musical Interaction

Music is a natural partner to human-computer interaction, offering tasks and use cases for novel forms of interaction. The richness of the relationship between a performer and their instrument in expressive musical performance can provide valuable insight to human-computer interaction (HCI) researchers interested in applying these forms of deep interaction to other fields. Despite the longstanding connection between music and HCI, it is not an automatic one, and its history arguably points to as many differences as it does overlaps. Music research and HCI research both encompass broad issues, and utilize a wide range of methods. In this chapter I discuss how the concept of embodied interaction can be one way to think about music interaction. I propose how the three “paradigms” of HCI and three design accounts from the interaction design literature can serve as a lens through which to consider types of music HCI. I use this conceptual framework to discuss three different musical projects—Haptic Wave, Form Follows Sound, and BioMuse

Timbre from Sound Synthesis and High-level Control Perspectives

International audienceExploring the many surprising facets of timbre through sound manipulations has been a common practice among composers and instrument makers of all times. The digital era radically changed the approach to sounds thanks to the unlimited possibilities offered by computers that made it possible to investigate sounds without physical constraints. In this chapter we describe investigations on timbre based on the analysis by synthesis approach that consists in using digital synthesis algorithms to reproduce sounds and further modify the parameters of the algorithms to investigate their perceptual relevance. In the first part of the chapter timbre is investigated in a musical context. An examination of the sound quality of different wood species for xylophone making is first presented. Then the influence of instrumental control on timbre is described in the case of clarinet and cello performances. In the second part of the chapter, we mainly focus on the identification of sound morphologies, so called invariant sound structures responsible for the evocations induced by environmental sounds by relating basic signal descriptors and timbre descriptors to evocations in the case of car door noises, motor noises, solid objects, and their interactions

Recruitment and Activation of Pancreatic Stellate Cells from the Bone Marrow in Pancreatic Cancer: A Model of Tumor-Host Interaction

BACKGROUND AND AIMS: Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC) contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS: Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA). Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS: GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC) population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS: This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that contribute to the activated PaSC population in chronic pancreatitis and pancreatic cancer have different phenotypes, and may play important roles in these diseases. Further, bone marrow transplantation may provide a useful model for the study of tumor-host interactions in cancer and pancreatitis

Performing Amateurism: A Study of Camgirls’ Work

International audienc

Discovery of Novel Human Breast Cancer MicroRNAs from Deep Sequencing Data by Analysis of Pri-MicroRNA Secondary Structures

MicroRNAs (miRNAs) are key regulators of gene expression and contribute to a variety of biological processes. Abnormal miRNA expression has been reported in various diseases including pathophysiology of breast cancer, where they regulate protumorigenic processes including vascular invasiveness, estrogen receptor status, chemotherapy resistance, invasion and metastasis. The miRBase sequence database, a public repository for newly discovered miRNAs, has grown rapidly with approximately >10,000 entries to date. Despite this rapid growth, many miRNAs have not yet been validated, and several others are yet to be identified. A lack of a full complement of miRNAs has imposed limitations on recognizing their important roles in cancer, including breast cancer. Using deep sequencing technology, we have identified 189 candidate novel microRNAs in human breast cancer cell lines with diverse tumorigenic potential. We further show that analysis of 500-nucleotide pri-microRNA secondary structure constitutes a reliable method to predict bona fide miRNAs as judged by experimental validation. Candidate novel breast cancer miRNAs with stem lengths of greater than 30 bp resulted in the generation of precursor and mature sequences in vivo. On the other hand, candidates with stem length less than 30 bp were less efficient in producing mature miRNA. This approach may be used to predict which candidate novel miRNA would qualify as bona fide miRNAs from deep sequencing data with approximately 90% accuracy

The joint influence of marital status, interpregnancy interval, and neighborhood on small for gestational age birth: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Interpregnancy interval (IPI), marital status, and neighborhood are independently associated with birth outcomes. The joint contribution of these exposures has not been evaluated. We tested for effect modification between IPI and marriage, controlling for neighborhood.</p> <p>Methods</p> <p>We analyzed a cohort of 98,330 live births in Montréal, Canada from 1997–2001 to assess IPI and marital status in relation to small for gestational age (SGA) birth. Births were categorized as subsequent-born with <it>short </it>(<12 months), <it>intermediate </it>(12–35 months), or <it>long </it>(36+ months) IPI, or as firstborn. The data had a 2-level hierarchical structure, with births nested in 49 neighborhoods. We used multilevel logistic regression to obtain adjusted effect estimates.</p> <p>Results</p> <p>Marital status modified the association between IPI and SGA birth. Being unmarried relative to married was associated with SGA birth for all IPI categories, particularly for subsequent births with <it>short </it>(odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31–1.95) and <it>intermediate </it>(OR 1.48, 95% CI 1.26–1.74) IPIs. Subsequent births had a lower likelihood of SGA birth than firstborns. <it>Intermediate </it>IPIs were more protective for married (OR 0.50, 95% CI 0.47–0.54) than unmarried mothers (OR 0.65, 95% CI 0.56–0.76).</p> <p>Conclusion</p> <p>Being unmarried increases the likelihood of SGA birth as the IPI shortens, and the protective effect of <it>intermediate </it>IPIs is reduced in unmarried mothers. Marital status should be considered in recommending particular IPIs as an intervention to improve birth outcomes.</p

Design Parameters to Control Synthetic Gene Expression in Escherichia coli

BACKGROUND:Production of proteins as therapeutic agents, research reagents and molecular tools frequently depends on expression in heterologous hosts. Synthetic genes are increasingly used for protein production because sequence information is easier to obtain than the corresponding physical DNA. Protein-coding sequences are commonly re-designed to enhance expression, but there are no experimentally supported design principles. PRINCIPAL FINDINGS:To identify sequence features that affect protein expression we synthesized and expressed in E. coli two sets of 40 genes encoding two commercially valuable proteins, a DNA polymerase and a single chain antibody. Genes differing only in synonymous codon usage expressed protein at levels ranging from undetectable to 30% of cellular protein. Using partial least squares regression we tested the correlation of protein production levels with parameters that have been reported to affect expression. We found that the amount of protein produced in E. coli was strongly dependent on the codons used to encode a subset of amino acids. Favorable codons were predominantly those read by tRNAs that are most highly charged during amino acid starvation, not codons that are most abundant in highly expressed E. coli proteins. Finally we confirmed the validity of our models by designing, synthesizing and testing new genes using codon biases predicted to perform well. CONCLUSION:The systematic analysis of gene design parameters shown in this study has allowed us to identify codon usage within a gene as a critical determinant of achievable protein expression levels in E. coli. We propose a biochemical basis for this, as well as design algorithms to ensure high protein production from synthetic genes. Replication of this methodology should allow similar design algorithms to be empirically derived for any expression system

Heritability of Self-reported Phobic Fear

Twin studies on fear and phobia suggest moderate genetic effects. However, results are inconclusive regarding the presence of dominant genetic effects and sex differences. Using an extended twin design, including male and female twins (n = 5,465) and their siblings (n = 1,624), we examined the genetic and environmental influences on blood-injury, social, and agoraphobic fear and investigated their interaction with sex and age. Data of spouses (n = 708) of twins were used to evaluate assortative mating for the three fear dimensions. Results showed that there was no assortative mating for blood-injury, social and agoraphobic fear. Resemblance between biological relatives could be explained by additive and non-additive genetic effects for blood-injury and agoraphobic fear in all participants, and social fear in participants aged 14–25 years. For social fear in participants aged 26–65 only additive genetic effects were detected. Broad-sense heritability estimates ranged from 36 to 51% and were similar for men and women

Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cells

<p>Abstract</p> <p>Background</p> <p>Viruses bind to specific cellular receptors in order to infect their hosts. The specific receptors a virus uses are important factors in determining host range, cellular tropism, and pathogenesis. For adenovirus, the existing model of entry requires two receptor interactions. First, the viral fiber protein binds Coxsackie and Adenovirus Receptor (CAR), its primary cellular receptor, which docks the virus to the cell surface. Next, viral penton base engages cellular integrins, coreceptors thought to be required exclusively for internalization and not contributing to binding. However, a number of studies reporting data which conflicts with this simple model have been published. These observations have led us to question the proposed two-step model for adenovirus infection.</p> <p>Results</p> <p>In this study we report that cells which express little to no CAR can be efficiently transduced by adenovirus. Using competition experiments between whole virus and soluble viral fiber protein or integrin blocking peptides, we show virus binding is not dependent on fiber binding to cells but rather on penton base binding cellular integrins. Further, we find that binding to low CAR expressing cells is inhibited specifically by a blocking antibody to integrin αvβ5, demonstrating that in these cells integrin αvβ5 and not CAR is required for adenovirus attachment. The binding mediated by integrin αvβ5 is extremely high affinity, in the picomolar range.</p> <p>Conclusions</p> <p>Our data further challenges the model of adenovirus infection in which binding to primary receptor CAR is required in order for subsequent interactions between adenovirus and integrins to initiate viral entry. In low CAR cells, binding occurs through integrin αvβ5, a receptor previously thought to be used exclusively in internalization. We show for the first time that integrin αvβ5 can be used as an alternate binding receptor.</p