Expression and role of BORIS/CTCFL in human cancer stem cells

Le cancer est défini comme la croissance incontrôlée des cellules dans le corps. Il est responsable de 20 % des décès en Europe. Plusieurs expériences montrent que les tumeurs sont issues et se développent grâce à un petit nombre de cellules, que l'on appelle cellules souches cancéreuses (CSC). Ces CSC sont également responsables de l'apparition de métastases et de la résistance aux médicaments anticancéreux. De ce fait, l'identification des gènes qui contribuent aux propriétés de ces CSC (comme la survie des tumeurs, les métastases et la résistance aux médicaments) est nécessaire pour mieux comprendre la biologie des cancers et d'améliorer la qualité des soins des patients avec un cancer. A ce jour, de nombreux marqueurs ont été proposés ainsi que de nouvelles thérapies ciblées contre les CSC. Toutefois, et malgré les énormes efforts de la recherche dans ce domaine, la quasi-totalité des marqueurs de CSC connus à ce jour sont aussi exprimés dans les cellules saines. Ce projet de recherche visait à trouver un nouveau candidat spécifique des CSC. Le gène BORIS (pour Brother of Regulator of Imprinted Sites), nommé aussi CTCFL (CTCF-like), semble avoir certaines caractéristiques de CSC et pourrait donc devenir une cible prometteuse pour le traitement du cancer. BORIS/CTCFL est une protéine nucléaire qui se lie à l'ADN, qui est exprimée dans les tissus normaux uniquement dans les cellules germinales et qui est réactivée dans un grand nombre de tumeurs. BORIS est impliqué dans la reprogrammation épigénétique au cours du développement et dans la tumorigenèse. En outre, des études récentes ont montré une association entre l'expression de BORIS et un mauvais pronostic chez des patients atteints de différents types de cancers. Nous avons développé une nouvelle technologie basée sur les Molecular Beacon pour cibler l'ARNm de BORIS et cela dans les cellules vivantes. Grâce à ce système expérimental, nous avons montré que seule une toute petite sous-population (0,02 à 5%) de cellules tumorales exprimait fortement BORIS. Les cellules exprimant BORIS ont pu être isolées et elles présentaient les caractéristiques de CSC, telles qu'une forte expression de hTERT et des gènes spécifiques des cellules souches (NANOG, SOX2 et OCT4). En outre, une expression élevée de BORIS a été mise en évidence dans des populations enrichies en CSC ('side population' et sphères). Ces résultats suggèrent que BORIS pourrait devenir un nouveau et important marqueur de CSC. Dans des études fonctionnelles sur des cellules de cancer du côlon et du sein, nous avons montré que le blocage de l'expression de BORIS altère largement la capacité de ces cellules à former des sphères, démontrant ainsi un rôle essentiel de BORIS dans l'auto- renouvellement des tumeurs. Nos expériences montrent aussi que BORIS est un facteur important qui régule l'expression de gènes jouant un rôle clé dans le développement et la progression tumorale, tels le gène hTERT et ceux impliqués dans les cellules souches, les CSC et la transition épithélio-mésenchymateuse (EMT). BORIS pourrait affecter la régulation de la transcription de ces gènes par des modifications épigénétiques et de manière différente en fonction du type cellulaire. En résumé, nos résultats fournissent la preuve que BORIS peut être classé comme un gène marqueur de cellules souches cancéreuse et révèlent un nouveau mécanisme dans lequel BORIS jouerait un rôle important dans la carcinogénèse. Cette étude ouvre de nouvelles voies pour mieux comprendre la biologie de la progression tumorale et offre la possibilité de développement de nouvelles thérapies anti-tumorales et anti-CSC avec BORIS comme molécule cible. - Cancer is defined as the uncontrolled growth of cells in the body. It causes 20% of deaths in the European region. Current evidences suggest that tumors originate and are maintained thanks to a small subset of cells, named cancer stems cells (CSCs). These CSCs are also responsible for the appearance of metastasis and therapeutic resistance. Consequently, the identification of genes that contribute to the CSC properties (tumor survival, metastasis and therapeutic resistance) is necessary to better understand the biology of malignant diseases and to improve care management. To date, numerous markers have been proposed to use as new CSC- targeted therapies. Despite the enormous efforts in research, almost all of the known CSCs markers are also expressed in normal cells. This project aimed to find a new CSC-specific candidate. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA binding protein involves in epigenetic reprogramming in normal development and in tumorigenesis. Recent studies have shown an association of BORIS expression with a poor prognosis in different types of cancer patients. Therefore, BORIS seems to have the same characteristics of CSCs markers and it could be a promising target for cancer therapy. BORIS is normally expressed only in germinal cells and it is re-expressed in a wide variety of tumors. We developed a new molecular beacon-based technology to target BORIS mRNA expressing cells. Using this system, we showed that the BORIS expressing cells are only a small subpopulation (0.02-5%) of tumor cells. The isolated BORIS expressing cells exhibited the characteristics of CSCs, with high expression of hTERT and stem cell genes (NANOG, SOX2 and OCT4). Furthermore, high BORIS expression was observed in the CSC-enriched populations (side population and spheres). These results suggest that BORIS might be a novel and powerful CSCs marker. In functional studies, we observed that BORIS knockdown significantly impairs the capacity to form spheres in colon and breast cancer cells, thus demonstrating a critical role of BORIS in the self-renewal of tumors. The results showed in the functional analysis indicate that BORIS is an important factor that regulates the expression of key-target genes for tumor development and progression, such as hTERT, stem cells, CSCs markers and EMT (epithelial mesenchymal transition)-related marker genes. BORIS could affect the transcriptional regulation of these genes by epigenetic modification and in a cell type dependent manner. In summary, our results support the evidence that BORIS can be classified as a cancer stem cell marker gene and reveal a novel mechanism in which BORIS would play a critical role in tumorigenesis. This study opens new prospective to understand the biology of tumor development and provides opportunities for potential anti-tumor drugs.

On fast-decodable space-time block codes

We focus on full-rate, fast-decodable space–time block codes (STBCs) for 2 x 2 and 4 x 2 multiple-input multiple-output (MIMO) transmission. We first derive conditions and design criteria for reduced-complexity maximum-likelihood (ML) decodable 2 x 2 STBCs, and we apply them to two families of codes that were recently discovered. Next, we derive a novel reduced-complexity 4 x 2 STBC, and show that it outperforms all previously known codes with certain constellations.

Generalized low-density codes with BCH constituents for full-diversity near-outage performance

A new graph-based construction of generalized low density codes (GLD-Tanner) with binary BCH constituents is described. The proposed family of GLD codes is optimal on block erasure channels and quasi-optimal on block fading channels. Optimality is considered in the outage probability sense. Aclassical GLD code for ergodic channels (e.g., the AWGN channel,the i.i.d. Rayleigh fading channel, and the i.i.d. binary erasure channel) is built by connecting bitnodes and subcode nodes via a unique random edge permutation. In the proposed construction of full-diversity GLD codes (referred to as root GLD), bitnodes are divided into 4 classes, subcodes are divided into 2 classes, and finally both sides of the Tanner graph are linked via 4 random edge permutations. The study focuses on non-ergodic channels with two states and can be easily extended to channels with 3 states or more.

Tractament lexicogràfic dels adjectius: aspectes a considerar

La informació gramatical més habitual de les entrades en un diccionari es basa quasi exclusivament en consignar la categoria sintàctica dels mots. Aquest plantejament suposa una parcel·lació massa vaga de les unitats lingüístiques, atès que en l'ús i la combinació entre elles hi entren en joc altres característiques, les quals porten a subclassificacions més precises a l'interior de les categories gramaticals. Un plantejament lexicogràfic que presenti un tractament detallat de les categories quant a les seves subclasses possibles és, a més d'útil en l'elaboració de diccionaris per a parlants de llengua estrangera, necessari també en diccionaris per a parlants natius de la llengua si, tal com és de suposar, l'ús que s'espera d'un diccionari va més enllà de la simple consulta del significat dels mots.En aquest article s'analitzen alguns dels punts que cal que els diccionaris tinguin en compte per a la descripció de l'ús real dels adjectius, es revisa quin és el tractament que reben en el diccionari pres com a font de referència (Diccionari de la Llengua Catalana (1994), d'Enciclopèdia Catalana) i s'esbossa una proposta de tractament per poder donar compte d'aquests aspectes. L'interès recau tant en qüestions d'ordre superficial dels constituents (la posició típica de les unitats), com aspectes sintàctics (la capacitat predicativa dels elements, la subcategorització de complements), així com també aspectes de tipus semàntic (la relació entre les denotacions de l'adjectiu i el substantiu, la facultat de graduabilitat dels adjectius).

L'Impacte dels diaris gratuïts sobre els diaris de pagament

Com a manera d’analitzar l’efecte de les innovacions que contínuamentexperimenta el món actual, hem cregut interessant analitzar l’impacte deldiaris gratuïts o premsa gratuïta sobre els diaris de pagament o premsatradicional, ja que creiem que, tot i que tan sols representa un petit canvien un àmbit molt concret com és el de la premsa, pot significar un mirall enel que fixar-se per altres sectors d’àmbit tradicionalment privat.Avui dia, des de fa ja uns anys, quan agafes el metro o l’autobús cada matíper anar al treball o a la universitat veiem que gairebé tothom té und’aquests diaris gratuïts a la mà (Qué!, Metro, 20 Minutos, ADN...) que elshi acaben de donar a l’entrada de l’estació. Veient això s’ens van plantejaruna sèrie de preguntes: la gent que llegeix diaris gratuïts, llegeix també lapremsa tradicional? L’aparició dels diaris gratuïts, ha fet reduir el nombre delectors de premsa de pagament? El que volem esbrinar és si aquests noustipus de diaris són una amenaça o més aviat són complementaris als diarisde pagament. La pregunta que volem respondre és: Quin ha estat l’impactedels diaris gratuïts sobre els diaris de pagament.Al llarg del treball veurem que l’entrada al mercat d’aquest nou tipus depremsa no ha suposat una amenaça pels diaris tradicionals, com potsemblar en un principi. Podrem comprovar que pel que fa al nombre delectors l’impacte és gairebé nul, és a dir, és veritat que els diaris depagament han patit un estancament en quant a nombre de lectors però noha afectat quasi bé gens als beneficis d’aquests. Tambè veurem, que és enel terreny de la publicitat on realment competeixen els dos tipus de diarisaixí com tambè, que la situació és diferent al nostre entorn respecte a laresta del món.

On the Properties and Cosmology of Q-balls

The properties and cosmological importance of a class of non-topological solitons, Q-balls, are studied. Aspects of Q-ball solutions and Q-ball cosmology discussed in the literature are reviewed. Q-balls are particularly considered in the Minimal Supersymmetric Standard Model with supersymmetry broken by a hidden sector mechanism mediated by either gravity or gauge interactions. Q-ball profiles, charge-energy relations and evaporation rates for realistic Q-ball profiles are calculated for general polynomial potentials and for the gravity mediated scenario. In all of the cases, the evaporation rates are found to increase with decreasing charge. Q-ball collisions are studied by numerical means in the two supersymmetry breaking scenarios. It is noted that the collision processes can be divided into three types: fusion, charge transfer and elastic scattering. Cross-sections are calculated for the different types of processes in the different scenarios. The formation of Q-balls from the fragmentation of the Aflieck-Dine -condensate is studied by numerical and analytical means. The charge distribution is found to depend strongly on the initial energy-charge ratio of the condensate. The final state is typically noted to consist of Q- and anti-Q-balls in a state of maximum entropy. By studying the relaxation of excited Q-balls the rate at which excess energy can be emitted is calculated in the gravity mediated scenario. The Q-ball is also found to withstand excess energy well without significant charge loss. The possible cosmological consequences of these Q-ball properties are discussed.

Coordination et décentralisation des règles budgétaires dans une structure fédéraliste : le cas des cantons suisses

La coordination des politiques budgétaires entre collectivités publiques se heurte à leur souveraineté individuelle. Les règles budgétaires indépendamment adoptées peuvent potentiellement aller à l'encontre des besoins généraux de stabilisation macroéconomique. En utilisant l'exemple des cantons suisses, cette contribution analyse la possibilité de dégager une politique anti-cyclique lorsque les collectivités locales se dotent de règles les contraignant à un équilibre budgétaire ou à un quasi-équilibre. On montre que, dotées ou non de règles, les collectivités adoptent généralement un comportement pro-cyclique. Toutefois, ce comportement peut être contrecarré si le gouvernement central instrumentalise la péréquation financière verticale au profit de la stabilisation.

Government Spending and Re-election

Does additional government spending improve the electoral chances of incumbent political parties? This paper provides the first quasi-experimental evidence on this question. Our research design exploits discontinuities in federal funding to local governments in Brazil around several population cutoffs over the period 1982-1985. We find that extra fiscal transfers resulted in a 20% increase in local government spending per capita, and an increase of about 10 percentage points in the re-election probability of local incumbent parties. We also find positive effects of the government spending on education outcomes and earnings, which we interpret as indirect evidence of public service improvements. Together, our results provide evidence that electoral rewards encourage incumbents to spend part of additional revenues on public services valued by voters, a finding in line with agency models of electoral accountability.

Human milk for neonatal pain relief during ophthalmoscopy

Ophthalmoscopy performed for the early diagnosis of retinopathy of prematurity (ROP) is painful for preterm infants, thus necessitating interventions for minimizing pain. The present study aimed to establish the effectiveness of human milk, compared with sucrose, for pain relief in premature infants subjected to ophthalmoscopy for the early diagnosis of ROP. This investigation was a pilot, quasi-experimental study conducted with 14 premature infants admitted to the neonatal intensive care unit (NICU) of a university hospital. Comparison between the groups did not yield a statistically significant difference relative to the crying time, salivary cortisol, or heart rate (HR). Human milk appears to be as effective as sucrose in relieving acute pain associated with ophthalmoscopy. The study’s limitations included its small sample size and lack of randomization. Experimental investigations with greater sample power should be performed to reinforce the evidence found in the present study.

Knowledge and attitudes of nurses towards alcohol and related problems: the impact of an educational intervention

An exploratory study of quasi-experimental approach that aimed to verify the impact of an educational intervention on attitudes and knowledge of nurses towards alcohol use and associated problems. The sample included 185 nurses, divided into two groups: 84 submitted to a training course and formed the experimental group. Data were collected through a knowledge survey and an attitude scale. The attitudes of the participants of both groups were positive. There were no significant differences between groups in relation to knowledge. The strongest predictors of positive attitudes were possessed preparation to act with chemical dependents (OR = 2.18), "have received increased workload during graduation on the theme, 'alcohol and other drugs'" (OR = 1.70), and "completed graduate school" (OR = 2.59). The educational intervention had a positive impact on the attitudes of nurses towards alcoholics, work and interpersonal relationships with such clientele.

Effectiveness of prayer in reducing anxiety in cancer patients

Objective: To evaluate the effect of prayer on anxiety in cancer patients undergoing chemotherapy. Method: Quasi-experimental study, with pre and post-intervention. Twenty patients admitted to treatment of continuous intravenous chemotherapy were recruited. The volunteers were evaluated through interviews using a questionnaire of sociodemographic, clinical and spiritual characteristics, the Index of Religiosity Duke University and the State-Trait Anxiety Inventory. Vital signs were measured and collected salivary cortisol. The intervention was applied prayer and data collection occurred in three phases: first collection (baseline), pre and post-intervention. Results: The data found between the pre and post-intervention samples showed different statistically significant for state anxiety (p= <0.00), blood pressure (systolic, p=0.00, diastolic, p=<0.00) and respiratory rate (p=0.04). Conclusion: Prayer, therefore, proved to be an effective strategy in reducing the anxiety of the patient undergoing chemotherapy.




The influence of institutionalization on the perception of autonomy and quality of life in old people

Objective To evaluate the influence exercised by institutionalization on the autonomy and perception of quality of life among the institutionalized elderly. Method The study is quasi-experimental (interrupted time series) and longitudinal. The sample is composed for 104 elderly people who went into a three nursing home in Santander, Spain. To assess the quality of life and dependence two scales were used: the Barthel Index and Lawton Index. Results There was an important relationship between autonomy and independence and their deterioration due to their institutionalisation, such as the physical and social aspects. Conclusion It´s important to point out that the dependence of the elderly is a complex phenomenon, which admits many types of intervention, including the customary ones referring to more classic welfare actions which tend to supplant the absence of autonomy in everyday life by facilitating services and attention to make up for this need, without having to resort to institutionalization.

Educational intervention on malignant hyperthermia with nursing professionals of the operating room

OBJECTIVE To evaluate the effectiveness of an educational intervention on malignant hyperthermia with operating room nurses. METHOD A quasi-experimental study, aimed at an educational intervention of short duration with the nursing staff in the operating room of the institution hosting the research in the city of São Paulo, with the participation of 96 professionals. Pre-intervention tests and post-intervention tests were applied, which consisted of a lecture followed by simulation. RESULTS Considering the overall results of the intervention, there was a statistically significant difference (p<0.00). After the educational intervention, there was an increase of the minimum and maximum scores, and average growth of 2.64 points in the knowledge of professionals when compared to the previous step. CONCLUSION The educational intervention strategy favors the concept of the content developed by everyone involved and qualifies professionals to work safely.

Effectiveness Of 2% And 4% Papain Gels In The Healing Of Venous Ulcers

OBJECTIVE To analyze the effectiveness of 2% and 4% papain gels in tissue repair of venous ulcers. METHOD Quasi-experimental study with consecutive sample of 16 patients with 30 venous ulcers treated at the outpatient clinic of a teaching hospital, from April to November in 2011, using a form for clinical assessment of the patient and its lesion. Variables were analyzed by Wilcoxon and McNemar test (p < 0.05). RESULTS Most participants were female; aged between 51 and 59 years; obese; with hypertension. Regarding ulcers, there was an average decrease of 7.9 cm2 (50% of its original size) in 90 days; 20% of the ulcers completely healed within 56.67 days. There was an increase in epithelialization, significant reduction in the slough and edema, improved depth, in the type and amount of exudate (p < 0.0001). CONCLUSION 2% and 4% papain gels were effective in healing venous ulcers.

What do outside experts bring to a committee? Evidence from the Bank of England

We test whether outside experts have information not available to insiders by usingthe voting record of the Bank of England's Monetary Policy Committee. Memberswith more private information should vote more often against conventional wisdom,which we measure as the average belief of market economists about future interest rates. We find evidence that external members indeed have information notavailable to internals, but also use a quasi-natural experiment to show they mayexaggerate their expertise to obtain reappointment. This implies that an optimalcommittee, even outside monetary policy, should potentially include outsiders, butneeds to manage career concerns.