Aptamers against the β-conglutin allergen: Insights into the behavior of the shortest multimeric (intra)molecular dna gquadruplex

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed

The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/

Ultrasensitive, rapid and inexpensive detection of DNA using paper based lateral flow assay

Sensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for use at the point-of-need are critical for the emerging field of personalised medicine for which companion diagnostics are essential, as well as for application in low resource settings. Here we report on the development of a point-of-care nucleic acid lateral flow test for the direct detection of isothermally amplified DNA. The recombinase polymerase amplification method is modified slightly to use tailed primers, resulting in an amplicon with a duplex flanked by two single stranded DNA tails. This tailed amplicon facilitates detection via hybridisation to a surface immobilised oligonucleotide capture probe and a gold nanoparticle labelled reporter probe. A detection limit of 1 7 10−11 M (190 amol), equivalent to 8.67 7 105 copies of DNA was achieved, with the entire assay, both amplification and detection, being completed in less than 15 minutes at a constant temperature of 37 \ub0C. The use of the tailed primers obviates the need for hapten labelling and consequent use of capture and reporter antibodies, whilst also avoiding the need for any post-amplification processing for the generation of single stranded DNA, thus presenting an assay that can facilely find application at the point of need

Large-scale geo-facial image analysis

While face analysis from images is a well-studied area, little work has explored the dependence of facial appearance on the geographic location from which the image was captured. To fill this gap, we constructed GeoFaces, a large dataset of geotagged face images, and used it to examine the geo-dependence of facial features and attributes, such as ethnicity, gender, or the presence of facial hair. Our analysis illuminates the relationship between raw facial appearance, facial attributes, and geographic location, both globally and in selected major urban areas. Some of our experiments, and the resulting visualizations, confirm prior expectations, such as the predominance of ethnically Asian faces in Asia, while others highlight novel information that can be obtained with this type of analysis, such as the major city with the highest percentage of people with a mustache

Single-Molecule Imaging of an in Vitro-Evolved RNA Aptamer Reveals Homogeneous Ligand Binding Kinetics

Many studies of RNA folding and catalysis have revealed conformational heterogeneity, metastable folding intermediates, and long-lived states with distinct catalytic activities. We have developed a single-molecule imaging approach for investigating the functional heterogeneity of in vitro-evolved RNA aptamers. Monitoring the association of fluorescently labeled ligands with individual RNA aptamer molecules has allowed us to record binding events over the course of multiple days, thus providing sufficient statistics to quantitatively define the kinetic properties at the single-molecule level. The ligand binding kinetics of the highly optimized RNA aptamer studied here displays a remarkable degree of uniformity and lack of memory. Such homogeneous behavior is quite different from the heterogeneity seen in previous single-molecule studies of naturally derived RNA and protein enzymes. The single-molecule methods we describe may be of use in analyzing the distribution of functional molecules in heterogeneous evolving populations or even in unselected samples of random sequences

Obstáculos para la movilidad académica con el programa Erasmus+: Diferencias entre grados universitarios [Barriers to academic mobility with Erasmus+ programme: Differences between bachelor degrees]

Pese al interés creciente que presenta la movilidad académica internacional de los estudiantes universitarios europeos para su inserción profesional posterior, el porcentaje de estudiantes españoles que participan en el programa Erasmus es todavía pequeño. El objetivo de este trabajo fue determinar los principales obstáculos para la movilidad Erasmus percibidos por estudiantes de grado que no han participado en este programa, valorando la existencia de diferencias en función del grado (Sanitario vs. Ciencias Sociales). Se utilizó una encuesta auto-administrada elaborada para un estudio europeo previo en el que participó España. Los resultados muestran el impacto, a nivel general, de la falta de información sobre temas relevantes como: la calidad de la educación en el extranjero, o cómo van a ser evaluados, así como, las barreras económicas por becas insuficientes y retrasos en el pago de las mismas. Los obstáculos que mejor diferencian a los estudiantes de ambos grados están relacionados con la ordenación académica del grado, en concreto, bajo nivel de formación en inglés y presencia de asignaturas anuales, además de características personales del estudiante. Para incrementar la participación, se debería incidir en informar más y comunicar mejor además de incluir modificaciones en el programa académico de los grados que faciliten la movilidad internacional. [Despite the growing interest that presents academic international mobility for European University students for their later in life job prospects, the rate of Spanish students participating in the Erasmus programme is still small. The objective of this research was to determine the main barriers perceived by bachelor students who had not participated in the Erasmus programme assessing the differences between two bachelor degrees (Health vs. Social Sciences). A self-administered survey including reasons not to participate was used that had been set up for a previous European study including Spain. Results reveal the overall impact of lack of information on relevant issues such as the quality of university education system abroad and how they will be evaluated as well as financial barriers such as insufficient Erasmus grants or delays in the first grant payment. The barriers that better differentiate both bachelor degrees students are related to the bachelors’ curriculum i.e. insufficient training in English and presence of annual (vs. semester) courses as well as personal features. To increase participation, the focus should be on improving information and communication both on academic and financial issues, and changes in the bachelors’ curricula.

DNA Copy Number Changes in Human Malignant Fibrous Histiocytomas by Array Comparative Genomic Hybridisation

BACKGROUND: Malignant fibrous histiocytomas (MFHs), or undifferentiated pleomorphic sarcomas, are in general high-grade tumours with extensive chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, as well as novel gene targets of potential importance for MFH development and/or progression, we have analysed DNA copy number changes in 33 MFHs using microarray-based comparative genomic hybridisation (array CGH). PRINCIPAL FINDINGS: In general, the tumours showed numerous gains and losses of large chromosomal regions. The most frequent minimal recurrent regions of gain were 1p33-p32.3, 1p31.3-p31.2 and 1p21.3 (all gained in 58% of the samples), as well as 1q21.2-q21.3 and 20q13.2 (both 55%). The most frequent minimal recurrent regions of loss were 10q25.3-q26.11, 13q13.3-q14.2 and 13q14.3-q21.1 (all lost in 64% of the samples), as well as 2q36.3-q37.2 (61%), 1q41 (55%) and 16q12.1-q12.2 (52%). Statistical analyses revealed that gain of 1p33-p32.3 and 1p21.3 was significantly associated with better patient survival (P = 0.021 and 0.046, respectively). Comparison with similar array CGH data from 44 leiomyosarcomas identified seven chromosomal regions; 1p36.32-p35.2, 1p21.3-p21.1, 1q32.1-q42.13, 2q14.1-q22.2, 4q33-q34.3, 6p25.1-p21.32 and 7p22.3-p13, which were significantly different in copy number between the MFHs and leiomyosarcomas. CONCLUSIONS: A number of recurrent regions of gain and loss have been identified, some of which were associated with better patient survival. Several specific chromosomal regions with significant differences in copy number between MFHs and leiomyosarcomas were identified, and these aberrations may be used as additional tools for the differential diagnosis of MFHs and leiomyosarcomas

Low Complexity Regularization of Linear Inverse Problems

Inverse problems and regularization theory is a central theme in contemporary signal processing, where the goal is to reconstruct an unknown signal from partial indirect, and possibly noisy, measurements of it. A now standard method for recovering the unknown signal is to solve a convex optimization problem that enforces some prior knowledge about its structure. This has proved efficient in many problems routinely encountered in imaging sciences, statistics and machine learning. This chapter delivers a review of recent advances in the field where the regularization prior promotes solutions conforming to some notion of simplicity/low-complexity. These priors encompass as popular examples sparsity and group sparsity (to capture the compressibility of natural signals and images), total variation and analysis sparsity (to promote piecewise regularity), and low-rank (as natural extension of sparsity to matrix-valued data). Our aim is to provide a unified treatment of all these regularizations under a single umbrella, namely the theory of partial smoothness. This framework is very general and accommodates all low-complexity regularizers just mentioned, as well as many others. Partial smoothness turns out to be the canonical way to encode low-dimensional models that can be linear spaces or more general smooth manifolds. This review is intended to serve as a one stop shop toward the understanding of the theoretical properties of the so-regularized solutions. It covers a large spectrum including: (i) recovery guarantees and stability to noise, both in terms of $\ell^2$-stability and model (manifold) identification; (ii) sensitivity analysis to perturbations of the parameters involved (in particular the observations), with applications to unbiased risk estimation ; (iii) convergence properties of the forward-backward proximal splitting scheme, that is particularly well suited to solve the corresponding large-scale regularized optimization problem