A genomic island present along the bacterial chromosome of the Parachlamydiaceae UWE25, an obligate amoebal endosymbiont, encodes a potentially functional F-like conjugative DNA transfer system.

BACKGROUND: The genome of Protochlamydia amoebophila UWE25, a Parachlamydia-related endosymbiont of free-living amoebae, was recently published, providing the opportunity to search for genomic islands (GIs). RESULTS: On the residual cumulative G+C content curve, a G+C-rich 19-kb region was observed. This sequence is part of a 100-kb chromosome region, containing 100 highly co-oriented ORFs, flanked by two 17-bp direct repeats. Two identical gly-tRNA genes in tandem are present at the proximal end of this genetic element. Several mobility genes encoding transposases and bacteriophage-related proteins are located within this chromosome region. Thus, this region largely fulfills the criteria of GIs. The G+C content analysis shows that several modules compose this GI. Surprisingly, one of them encodes all genes essential for F-like conjugative DNA transfer (traF, traG, traH, traN, traU, traW, and trbC), involved in sex pilus retraction and mating pair stabilization, strongly suggesting that, similarly to the other F-like operons, the parachlamydial tra unit is devoted to DNA transfer. A close relatedness of this tra unit to F-like tra operons involved in conjugative transfer is confirmed by phylogenetic analyses performed on concatenated genes and gene order conservation. These analyses and that of gly-tRNA distribution in 140 GIs suggest a proteobacterial origin of the parachlamydial tra unit. CONCLUSIONS: A GI of the UWE25 chromosome encodes a potentially functional F-like DNA conjugative system. This is the first hint of a putative conjugative system in chlamydiae. Conjugation most probably occurs within free-living amoebae, that may contain hundreds of Parachlamydia bacteria tightly packed in vacuoles. Such a conjugative system might be involved in DNA transfer between internalized bacteria. Since this system is absent from the sequenced genomes of Chlamydiaceae, we hypothesize that it was acquired after the divergence between Parachlamydiaceae and Chlamydiaceae, when the Parachlamydia-related symbiont was an intracellular bacteria. It suggests that this heterologous DNA was acquired from a phylogenetically-distant bacteria sharing an amoebal vacuole. Since Parachlamydiaceae are emerging agents of pneumonia, this GI might be involved in pathogenicity. In future, conjugative systems might be developed as genetic tools for Chlamydiales.

Hormone signalling crosstalk in plant growth regulation.

The remarkable plasticity of plant ontogeny is shaped by hormone pathways, which not only orchestrate intrinsic developmental programs, but also convey environmental inputs. Several classes of plant hormones exist, and among them auxin, brassinosteroid and gibberellin are central for the regulation of growth in general and of cell elongation in particular. Various growth phenomena can be modulated by each of the three hormones, in a sometimes synergistic fashion, suggesting physiological redundancy and/or crosstalk between the different pathways. Whether this means that they target a common and unique transcriptome module, or rather separate growth-promoting transcriptome modules, remains unclear, however. Nevertheless, while surprisingly few molecular mediators of direct crosstalk in the proper sense have been isolated, evidence is accumulating for complex cross-regulatory relations between hormone pathways at the level of transcription, as exemplified in root meristem growth. The growing number of available genome sequences from the green lineage offers first glimpses at the evolution of hormone pathways, which can aid in understanding the multiple relationships observed between these pathways in angiosperms. The available analyses suggest that auxin, gibberellin and brassinosteroid signalling arose during land plant evolution in this order, correlating with increased morphological complexity and possibly conferring increased developmental flexibility.

Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026. © 2013 Swiss Institute of Bioinformatics. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A developmental framework for endodermal differentiation and polarity.

The endodermis is a root cell layer common to higher plants and of fundamental importance for root function and nutrient uptake. The endodermis separates outer (peripheral) from inner (central) cell layers by virtue of its Casparian strips, precisely aligned bands of specialized wall material. Here we reveal that the membrane at the Casparian strip is a diffusional barrier between the central and peripheral regions of the plasma membrane and that it mediates attachment to the extracellular matrix. This membrane region thus functions like a tight junction in animal epithelia, although plants lack the molecular modules that establish tight junction in animals. We have also identified a pair of influx and efflux transporters that mark both central and peripheral domains of the plasma membrane. These transporters show opposite polar distributions already in meristems, but their localization becomes refined and restricted upon differentiation. This "central-peripheral" polarity coexists with the apical-basal polarity defined by PIN proteins within the same cells, but utilizes different polarity determinants. Central-peripheral polarity can be already observed in early embryogenesis, where it reveals a cellular polarity within the quiescent center precursor cell. A strict diffusion block between polar domains is common in animals, but had never been described in plants. Yet, its relevance to endodermal function is evident, as central and peripheral membranes of the endodermis face fundamentally different root compartments. Further analysis of endodermal transporter polarity and manipulation of its barrier function will greatly promote our understanding of plant nutrition and stress tolerance in roots.

Aproximació a la metrologia ibèrica (segles V-II aC)

En aquest treball presentem l’estat de la recerca de la metrologia ibèrica aplicada a l’arquitectura. S’analitza un conjunt ample d’assentaments, amb una cronologia que abasta des de l’ibèric ple fins a la romanització, i un àmbit geogràfic que comprèn tot el nord-est de la península Ibèrica. L’anàlisi metrològica de l’urbanisme i els sistemes defensius ibèrics ens han permès identificar dos possibles sistemes de mesures propis de les comunitats ibèriques. La definició de les proporcions geomètriques emprades a les construccions, així com les propostes de restitució d’aquestes, ens permet identificar una repetició de mòduls que mostren el probable ús d’eines de mesura. Conjuntament, hem comprovat que tant l’aplicació d’unitats constructives mediterrànies com dels principals sistemes de proporcions indiquen que el món ibèric català es troba immers dintre dels principals corrents característics de la koiné mediterrània entre els segles V i II aC

Actin cables and the exocyst form two independent morphogenesis pathways in the fission yeast.

Cell morphogenesis depends on polarized exocytosis. One widely held model posits that long-range transport and exocyst-dependent tethering of exocytic vesicles at the plasma membrane sequentially drive this process. Here, we describe that disruption of either actin-based long-range transport and microtubules or the exocyst did not abolish polarized growth in rod-shaped fission yeast cells. However, disruption of both actin cables and exocyst led to isotropic growth. Exocytic vesicles localized to cell tips in single mutants but were dispersed in double mutants. In contrast, a marker for active Cdc42, a major polarity landmark, localized to discreet cortical sites even in double mutants. Localization and photobleaching studies show that the exocyst subunits Sec6 and Sec8 localize to cell tips largely independently of the actin cytoskeleton, but in a cdc42 and phospholipid phosphatidylinositol 4,5-bisphosphate (PIP₂)-dependent manner. Thus in fission yeast long-range cytoskeletal transport and PIP₂-dependent exocyst represent parallel morphogenetic modules downstream of Cdc42, raising the possibility of similar mechanisms in other cell types.

Shoulder pathology: estimating dominant upper-limb activity using 3D kinematic sensors.

Introduction. Quantification of daily upper-limb activity is a key determinant in evaluation of shoulder surgery. For a number of shoulder diseases, problem in performing daily activities have been expressed in terms of upper-limb usage and non-usage. Many instruments measure upper-limb movement but do not focus on the differentiations between the use of left or right shoulder. Several methods have been used to measure it using only accelerometers, pressure sensors or video-based analysis. However, there is no standard or widely used objective measure for upper-limb movement. We report here on an objective method to measure the movement of upper-limb and we examined the use of 3D accelerometers and 3D gyroscopes for that purpose. Methods. We studied 8 subjects with unilateral pathological shoulder (8 rotator cuff disease: 53 years old ± 8) and compared them to 18 control subjects (10 right handed, 8 left handed: 32 years old ± 8, younger than the patient group to be almost sure they don_t have any unrecognized shoulder pathology). The Simple Shoulder Test (SST) and Disabilities of the Arm and Shoulder Score (DASH) questionnaires were completed by each subject. Two modules with 3 miniature capacitive gyroscopes and 3 miniature accelerometers were fixed by a patch on the dorsal side of the distal humerus, and one module with 3 gyroscopes and 3 accelerometers were fixed on the thorax. The subject wore the system during one day (8 hours), at home or wherever he/she went. We used a technique based on the 3D acceleration and the 3D angular velocities from the modules attached on the humerus. Results. As expected, we observed that for the stand and sit postures the right side is more used than the left side for a healthy right-handed person(idem on the left side for a healthy left-handed person). Subjects used their dominant upper-limb 18% more than the non-dominant upper-limb. The measurements on patients in daily life have shown that the patient has used more his non affected and non dominant side during daily activity if the dominant side = affected shoulder. If the dominant side affected shoulder, the difference can be showed only during walking period. Discussion-Conclusion. The technique developed and used allowed the quantification of the difference between dominant and non dominant side, affected and unaffected upper-limb activity. These results were encouraging for future evaluation of patients with shoulder injuries, before and after surgery. The feasibility and patient acceptability of the method using body fixed sensors for ambulatory evaluation of upper limbs kinematics was shown.

Genomic islands: tools of bacterial horizontal gene transfer and evolution.

Abstract Bacterial genomes evolve through mutations, rearrangements or horizontal gene transfer. Besides the core genes encoding essential metabolic functions, bacterial genomes also harbour a number of accessory genes acquired by horizontal gene transfer that might be beneficial under certain environmental conditions. The horizontal gene transfer contributes to the diversification and adaptation of microorganisms, thus having an impact on the genome plasticity. A significant part of the horizontal gene transfer is or has been facilitated by genomic islands (GEIs). GEIs are discrete DNA segments, some of which are mobile and others which are not, or are no longer mobile, which differ among closely related strains. A number of GEIs are capable of integration into the chromosome of the host, excision, and transfer to a new host by transformation, conjugation or transduction. GEIs play a crucial role in the evolution of a broad spectrum of bacteria as they are involved in the dissemination of variable genes, including antibiotic resistance and virulence genes leading to generation of hospital 'superbugs', as well as catabolic genes leading to formation of new metabolic pathways. Depending on the composition of gene modules, the same type of GEIs can promote survival of pathogenic as well as environmental bacteria.

Deciphering the global organization of clustering in real complex networks

We uncover the global organization of clustering in real complex networks. To this end, we ask whether triangles in real networks organize as in maximally random graphs with given degree and clustering distributions, or as in maximally ordered graph models where triangles are forced into modules. The answer comes by way of exploring m-core landscapes, where the m-core is defined, akin to the k-core, as the maximal subgraph with edges participating in at least m triangles. This property defines a set of nested subgraphs that, contrarily to k-cores, is able to distinguish between hierarchical and modular architectures. We find that the clustering organization in real networks is neither completely random nor ordered although, surprisingly, it is more random than modular. This supports the idea that the structure of real networks may in fact be the outcome of self-organized processes based on local optimization rules, in contrast to global optimization principles.

Online teaching of inflammatory skin pathology by a French-speaking International University Network.

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

Comprehensive Statewide Transportation Model: Multimodal Investment Analysis Methodology Phase II, CTRE Project 02-126, 2001

The purposes of this report (Phase II of the project) are to specify in mathematical form the individual modules of the conceptual model developed in Phase I, to identify and evaluate sources of data for the model set, and to develop the transport networks necessary to support the models.

Wit Quiz. Plataforma de aprendizaje sobre dispositivos móviles

El artículo presenta el panorama actual de las nuevas tecnologías en el mundo de la educación.Del potencial que presentan las nuevas tecnologias y concretamente los dispositivos móviles, nace el proyecto KPAX, una plataforma tecnológica que soporte la incorporación de módulos independientes de aprendizaje basado en juegos.Wit Quiz es un caso práctico de dicho proyecto. Es un juego que integra las nuevas tecnologías con nuevas formas de aprendizaje informal. Se ha optado por una primera implementación sobre Iphone debido al éxito creciente de sus apps.La aplicación Wit Quiz ha sido desarrollada con cocoa, xcode y objective-c y permite una fácil gesión de sus contenidos gracias a la implementación de un servicio web.

Dynamic Runtime Variation and Branding in S60 Software

Diplomityössä tutkitaan keinoja brändätä ja varioida S60-ohjelmistoja dynaamisesti ja ajonaikaisesti. S60 on kehitysalusta, jota käyttävät useat puhelinvalmistajat ja heidän puhelimiaan käyttävät lukuisat eri operaattorit. Operaattorit haluavat puhelimiensa tai osan puhelimen sovelluksista erottuvan kilpailijoista heidän omalla brändillään ja tämän takia täytyy olla keinot joko koko puhelimen, tai valittujen sovellusten brändäykselle. Osa sovelluksista saatetaan haluta vaihtavan käytettyä brändiä sen käyttämien resurssien, kuten verkkopalvelimen, mukaan. Variointidataa tulee myös pystyä jakamaan eri sovellusten tai sovellusten osien kesken. Työssä esitellään Symbian käyttöjärjestelmä ja S60 kehitysympäristö, sekä pohditaan Symbianin turvallisuuskäytäntöjen tuomia haasteita variointidatan jakamiseen eri sovellusten välillä. Olemassaolevia variointitapoja tutkitaan työn mahdolliseksi pohjaksi. Työ sisältää esittelyn projektista, jossa kehitettiin erään S60 sovelluksen dynaaminen brändäystoteutus, joka myös mahdollistaa variointidatan jakamisen eri sovellusten kanssa.

Sobre un modelo constructivo de la arquitectura ibérica en territorio Ausetano

En este trabajo presentamos el estudio arquitectónico de un tipo de construcción identifi cado en el territorio ibérico ausetano. A partir del análisis constructivo de tres obras defensivas militares identifi cadas como murallas de compartimentos (Turó del Montgròs, Casol de Puigcastellet y l’Esquerda), planteamos una propuesta de restitución del diseño arquitectónico de estas construcciones basadas en el uso de formas geométricas simples y en la adición de módulos cuadrangulares.

Ydinvoimalan paineakun mallinnus

Tässä työssä on käytetty VTT:n ja Fortumin kehittämääAPROS simulaatio-ohjelmistoa vesi-ilma -täytteisen paineakun käyttäytymisen tutkimiseen. Tavoitteena oli tarkastella APROSin paineakkumallin käyttäytymistä alhaisessa lämpötilassa käyttäen 6-yhtälömallia sekä rakentaa vaihtoehtoiseksi laskentamenetelmäksi kaksi analyyttistä laskentamallia korvaamaan APROSin sisäinen laskenta. Kyseiset analyyttiset mallit ovat isentrooppinen ja isoterminen ja ne on rakennettu kokonaan käyttäen APROSin omia moduuleja. Työ sisältää APROSin version 5.06 sekä työn aikana kehitetyn kehitysversion vertailut eri alkulämpötiloista alkaneissa paisunnoissa, vertailun Pactelin purkaus¬kokeesta saadulla massavirralla sekä osion, jossa analyyttiset mallit on yhdistetty kokonaiseen Pactelin APROS-malliin. Myös purkauksen kulkeutumista primääripiirissä on tarkasteltu. Simulaatiot vahvistavat, että versiolla 5.06 on vaikeuksia paineen laskennassa, kun paisunnan alkulämpötila on alle 30 ºC. Kehitysversiossa painekäyttäytyminen on selvästi parantunut, mutta versio kärsii ongelmista, jotka liittyvät kaasun lämpötilan painumiseen APROSin sisäisten rajoitusten alapuolelleja tätä kautta ongelmiin materiaali¬ominaisuuksien ennustamisessa. Tämän johdosta APROSin kehitysversio päätyy erilaisiin tuloksiin myös tilanteissa, joissa alkuperäinen 5.06 ei kärsi alhaisen lämpötilan ongelmista. Analyyttisistä malleista isentrooppinen malli päätyy antamaan säännönmukaisesti muita malleja ja versioita alempia paineita. Isoterminen malli sen sijaan näyttää päätyvän version 5.06 kanssa melko samankaltaisiin tuloksiin. On kuitenkin muistettava, että kummatkin analyyttiset mallit olettavat kaasun olevan kuivaa ja jättävät massasiirron faasien välillä kokonaan huomiotta.