Predatory Bacteria: A Potential Ally against Multidrug-Resistant Gram-Negative Pathogens

Multidrug-resistant (MDR) Gram-negative bacteria have emerged as a serious threat to human and animal health. Bdellovibrio spp. and Micavibrio spp. are Gram-negative bacteria that prey on other Gram-negative bacteria. In this study, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on MDR Gram-negative clinical strains was examined. Although the potential use of predatory bacteria to attack MDR pathogens has been suggested, the data supporting these claims is lacking. By conducting predation experiments we have established that predatory bacteria have the capacity to attack clinical strains of a variety of ß-lactamase-producing, MDR Gram-negative bacteria. Our observations indicate that predatory bacteria maintained their ability to prey on MDR bacteria regardless of their antimicrobial resistance, hence, might be used as therapeutic agents where other antimicrobial drugs fail. © 2013 Kadouri et al

Tablon3: adaptación de una herramienta de gamificación al entorno de ejecución Python 3

En este trabajo se describe el proceso de adaptación del código de la herramienta de gamificación Tablon al lenguaje de programación Python 3. Como paso anterior a este proceso se analiza de manera exhaustiva el funcionamiento de la aplicación y se redacta una documentación que detalla la estructura, funcionamiento e implementación de la aplicación. En la documentación de esta herramienta se incluyen desde explicaciones detalladas del contenido de cada fichero hasta diagramas de diseño que representan la estructura de Tablon. También se recoge en este documento una explicación del proceso de conversión que se ha realizado para obtener la aplicación final Tablon3.This manuscript describes the process of adapting the code of the gamification tool Tablon to the Python 3 programming language. As a previous step to this process, the operation of the application is thoroughly analyzed and a documentation detailing the structure, operation and implementation of the application is written. This documentation includes detailed explanations of the content of each file, design diagrams that represent the structure of Tablon, etc. This document also includes an explanation of the conversion process that has been carried out to obtain the final Tablon3 application.Grado en Ingeniería Informátic

Creación de un paquete de análisis de series temporales para RStudio

En este trabajo se presenta el paquete CBJTSA para el lenguaje de programación R, el cual implementa distintas funciones para el análisis de series temporales mediante modelos ARIMA, completando las salidas de otros paquetes de R. Este paquete está enfocado al ámbito educativo, por lo que el objetivo del mismo será facilitar el acceso a herramientas de análisis de series temporales, usando este paquete como sustituto de otras herramientas más complejas y costosas. A lo largo de esta memoria se describen las distintas funciones que contiene el paquete con detalle, explicando su uso y las salidas que proporciona. Además, se incluye un ejemplo práctico de análisis de una serie temporal utilizando el paquete CBJTSA, para ilustrar su funcionamiento en un caso más específico.This paper presents the CBJTSA package for the R programming language, which implements different functions for the analysis of time series using ARIMA models, complementing the outputs of other R packages. This package is focused on the educational enviroment, so its objective is to facilitate access to time series analysis tools, using this package as a substitute for other more complex and expensive tools. Throughout this report, the different functions contained in the package are described in depth, explaining its use and the outputs it provides. In addition, a practical example of a time series analysis using the CBJTSA package is included to illustrate its operation in a more specific case.Departamento de Estadística e Investigación OperativaGrado en Estadístic

The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP

Vaults are ubiquitous ribonucleoprotein complexes involved in a diversity of cellular processes, including multidrug resistance, transport mechanisms and signal transmission. The vault particle shows a barrel-shaped structure organized in two identical moieties, each consisting of 39 copies of the major vault protein MVP. Earlier data indicated that vault halves can dissociate at acidic pH. The crystal structure of the vault particle solved at 8 Å resolution, together with the 2.1-Å structure of the seven N-terminal domains (R1–R7) of MVP, reveal the interactions governing vault association and provide an explanation for a reversible dissociation induced by low pH. The structural comparison with the recently published 3.5 Å model shows major discrepancies, both in the main chain tracing and in the side chain assignment of the two terminal domains R1 and R2

Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al

New Symmetries in Crystals and Handed Structures

For over a century, the structure of materials has been described by a combination of rotations, rotation-inversions and translational symmetries. By recognizing the reversal of static structural rotations between clockwise and counterclockwise directions as a distinct symmetry operation, here we show that there are many more structural symmetries than are currently recognized in right- or left-handed handed helices, spirals, and in antidistorted structures composed equally of rotations of both handedness. For example, though a helix or spiral cannot possess conventional mirror or inversion symmetries, they can possess them in combination with the rotation reversal symmetry. Similarly, we show that many antidistorted perovskites possess twice the number of symmetry elements as conventionally identified. These new symmetries predict new forms for "roto" properties that relate to static rotations, such as rotoelectricity, piezorotation, and rotomagnetism. They also enable symmetry-based search for new phenomena, such as multiferroicity involving a coupling of spins, electric polarization and static rotations. This work is relevant to structure-property relationships in all material structures with static rotations such as minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Desensitizing Inflation from the Planck Scale

A new mechanism to control Planck-scale corrections to the inflationary eta parameter is proposed. A common approach to the eta problem is to impose a shift symmetry on the inflaton field. However, this symmetry has to remain unbroken by Planck-scale effects, which is a rather strong requirement on possible ultraviolet completions of the theory. In this paper, we show that the breaking of the shift symmetry by Planck-scale corrections can be systematically suppressed if the inflaton field interacts with a conformal sector. The inflaton then receives an anomalous dimension in the conformal field theory, which leads to sequestering of all dangerous high-energy corrections. We analyze a number of models where the mechanism can be seen in action. In our most detailed example we compute the exact anomalous dimensions via a-maximization and show that the eta problem can be solved using only weakly-coupled physics.Comment: 34 pages, 3 figures

Exactly Marginal Deformations and Global Symmetries

We study the problem of finding exactly marginal deformations of N=1 superconformal field theories in four dimensions. We find that the only way a marginal chiral operator can become not exactly marginal is for it to combine with a conserved current multiplet. Additionally, we find that the space of exactly marginal deformations, also called the "conformal manifold," is the quotient of the space of marginal couplings by the complexified continuous global symmetry group. This fact explains why exactly marginal deformations are ubiquitous in N=1 theories. Our method turns the problem of enumerating exactly marginal operators into a problem in group theory, and substantially extends and simplifies the previous analysis by Leigh and Strassler. We also briefly discuss how to apply our analysis to N=2 theories in three dimensions.Comment: 23 pages, 2 figure

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)