Analysis of the genetic variation in Mycobacterium tuberculosis strains by multiple genome alignments

<p>Abstract</p> <p>Background</p> <p>The recent determination of the complete nucleotide sequence of several <it>Mycobacterium tuberculosis </it>(MTB) genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C), along with the genomes of laboratory strains (H37Rv and H37Ra), provides new insights on the mechanisms of adaptation of this bacterium to the human host.</p> <p>Findings</p> <p>The genetic variation found in six <it>M. tuberculosis </it>strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software <it>islandsanalyser</it>, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms.</p> <p>Conclusion</p> <p>The comparison of multiple genomes demonstrates that the <it>M. tuberculosis </it>genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.</p

The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination

A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome. This gene codifies a protein with ubiquitin ligase activity that regulates the activity of tumor protein p53 and is involved in important cellular processes such as DNA repair, cell cycle, cancer, and iron metabolism. Despite the critical role of HERC2 in these physiological and pathological processes, little is known about its relevance in vivo. Here, we described a mouse with targeted inactivation of the Herc2 gene. Homozygous mice were not viable. Distinct from other ubiquitin ligases that interact with p53, such as MDM2 or MDM4, p53 depletion did not rescue the lethality of homozygous mice. The HERC2 protein levels were reduced by approximately one-half in heterozygous mice. Consequently, HERC2 activities, including ubiquitin ligase and stimulation of p53 activity, were lower in heterozygous mice. A decrease in HERC2 activities was also observed in human skin fibroblasts from individuals with an Angelman-like syndrome that express an unstable mutant protein of HERC2. Behavioural analysis of heterozygous mice identified an impaired motor synchronization with normal neuromuscular function. This effect was not observed in p53 knockout mice, indicating that a mechanism independent of p53 activity is involved. Morphological analysis showed the presence of HERC2 in Purkinje cells and a specific loss of these neurons in the cerebella of heterozygous mice. In these animals, an increase of autophagosomes and lysosomes was observed. Our findings establish a crucial role of HERC2 in embryonic development and motor coordination

SEU Tests Performed on the Digital Communication System for LHC Cryogenic Instrumentation

The future LHC particle accelerator will use a large number of cryogenic sensors and actuators, most of which are located inside the machine tunnel and therefore in a radiation environment. These elements will communicate through a fieldbus. This paper reports the irradiation study carried out on WorldFIP fieldbus communication system. A digital communication system based on WorldFIP fieldbus protocol has been implemented and Single Event Effects (SEE) and Total Ionizing Dose (TID) radiation tests have been performed on it

Signal Conditioning for Cryogenic Thermometry in the LHC

Temperature measurement is a key issue in the LHC, as it will be used to regulate the cooling of the superconducting magnets. The compromise between available cooling power and the coil superconducting characteristics leads to a restricted temperature control band, around 1.9 K. An absolute accuracy DeltaT < 10 mK below 2.2 K, and DeltaT < 5 K above 25 K, is necessary. For resistive thermometers covering the full temperature range, and having a negative dR/dT sensitivity, this is typically equivalent to a relative accuracy DeltaR/R of 3 10**-3 over 3 resistance decades. Also, to limit the thermometer's self-heating, the sensing current must be limited to few muA. Furthermore, the radiation levels next to the accelerator are expected to degrade significantly the performance of conventional analogue electronics. As these stringent requirements are not met by commercial conditioners, three different architectures have been developed at CERN. The first compresses the input dynamic range using a logarithmic transfer function; the second partitions the input range into three linear regions; the third converts resistance linearly into the frequency of a square wave. They fulfil the above specifications and provide industrial robustness in terms of thermal drift, galvanic protection, and compact packaging, while optimising cost-to-performance ratio. This paper describes the principles of their design, compares their characteristics and shows results of field tests. Future developmens include ASIC versions, Fieldbus interfacing, and radiation tolerant re-design

Desarrollo de la metodología Lean Healthcare, como estrategia de mejoramiento continuo, que permita elevar el nivel de servicio prestado en el área de Imágenes diagnósticas del hospital Universitario de La Samaritana (HUS).

El área de Imágenes Diagnósticas es un área de apoyo para áreas como urgencias y hospitalización, es por eso, que el nivel de servicio prestado por dicha área cobra relevancia en el día a día de cualquier hospital de tercer nivel. La principal oportunidad de mejora identificada en la prestación de estos servicios de apoyo es el aumento del tiempo de ciclo de los procesos. Este hace referencia desde la generación de la orden del examen hasta la entrega de los resultados del mismo. Por ende, al existir poca eficiencia en la prestación de los servicios, esto se refleja en el tiempo total utilizado para el diagnóstico y atención de los pacientes. El objetivo principal del proyecto fue desarrollar la metodología Lean Healthcare, como estrategia de mejoramiento continuo en el área de Imágenes Diagnósticas del Hospital Universitario de La Samaritana (HUS). Los grupos de servicios analizados fueron TAC y procedimientos de radiología intervencionista, para los pacientes de urgencias y hospitalización. El desarrollo de esta metodología se dividió en 6 fases, así: i) caracterización de la situación actual, ii) mapeo del flujo de valor del proceso, iii) identificación de causas de desperdicios, iv) definición de estrategias Lean, v) implementación de estrategias a corto plazo y vi) evaluación del impacto de las estrategias de mejoramiento aplicadas. Dentro de los principales resultados obtenidos, está la validación de la metodología Lean Healthcare la cual permitió disminuir el porcentaje de tiempo que no agrega valor al proceso, mediante la reducción de mudas tales como: movimientos, tiempos de espera y sobre-procesoThe diagnostic imaging area is a support area for areas such as emergencies and hospitalization, that is why the level of service provided by this area is relevant in the day to day of any third level hospital. The main improvement opportunity identified in the provision of these support services is the increased cycle time of the processes. This refers from the generation of the exam order to the delivery of the test results. As a result, there is little efficiency in the provision of services, this is reflected in the total time used for diagnosis and care of patients. The main objective of the project was developing the Lean Healthcare methodology, as a strategy for continuous improvement in the diagnostic imaging area of the Hospital Universitario de La Samaritana (HUS). The groups of services analyzed were CT (Computed tomography) and interventional radiology procedures for emergency patients and hospitalization. The development of this methodology was divided into 6 phases, as follows: i) characterization of the current situation, ii) process value flow mapping, iii) identification of causes of waste, iv) definition of Lean strategies, v) implementation of Short-term strategies and vi) evaluation of the impact of the improvement strategies applied. Among the main results obtained, is the validation of the Lean Healthcare methodology, it allowed to reduce the percentage of time that does not add value to the process, through the reduction of waste such as: movements, waiting times and over-processing

Antifungal mechanisms by which a novel Pseudomonas aeruginosa phenazine toxin kills Candida albicans in biofilms

Pseudomonas aeruginosa produces several phenazines including the recently described 5-methyl-phenazine-1-carboxylic acid (5MPCA), which exhibits a novel antibiotic activity towards pathogenic fungi such as Candida albicans . Here we characterize the unique antifungal mechanisms of 5MPCA using its analogue phenazine methosulphate (PMS). Like 5MPCA, PMS induced fungal red pigmentation and killing. Mass spectrometry analyses demonstrated that PMS can be covalently modified by amino acids, a process that yields red derivatives. Furthermore, soluble proteins from C. albicans grown with either PMS or P. aeruginosa were also red and demonstrated absorbance and fluorescence spectra similar to that of PMS covalently linked to either amino acids or proteins in vitro , suggesting that 5MPCA modification by protein amine groups occurs in vivo . The red-pigmented C. albicans soluble proteins were reduced by NADH and spontaneously oxidized by oxygen, a reaction that likely generates reactive oxygen species (ROS). Additional evidence indicated that ROS generation precedes 5MPCA-induced fungal death. Reducing conditions greatly enhanced PMS uptake by C. albicans and killing. Since 5MPCA was more toxic than other phenazines that are not modified, such as pyocyanin, we propose that the covalent binding of 5MPCA promotes its accumulation in target cells and contributes to its antifungal activity in mixed-species biofilms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79382/1/j.1365-2958.2010.07414.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79382/2/MMI_7414_sm_Figures_Table.pd

Problema del school timetabling y algoritmos genéticos: una revisión

This paper shows an overview of the problem, “School Timetabling”, it treats first a definition of this problem, their classification, their computational complexity, and then it makes a review the different techniques which can be solved and the last one review one of these techniques such as genetic algorithms (GA), which was chosen to solution it. En este artículo se presenta de manera general el problema “School Timetabling”, se parte de una definición del mismo, su clasificación, su complejidad computacional, para luego entrar a revisar las diferentes técnicas con las cuales se puede solucionar el mismo y como último se entra a revisar una de estas técnicas como son los algoritmos genéticos (AG) que fue la escogida para darle solución