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Aim The aim of this study was to further advance our understanding of the species‐rich, and ecologically important angiosperm family Combretaceae to provide new insights into their evolutionary history. We assessed phylogenetic relationships in the family using target capture data and produced a dated phylogenetic tree to assess fruit dispersal modes and patterns of distribution. Location Tropical and subtropical regions. Time Period Cretaceous to present. Major Taxa Studied Family Combretaceae is a member of the rosid clade and comprises 10 genera and more than 500 species, predominantly assigned to generaCombretumandTerminalia, and occurring on all continents and in a wide range of ecosystems. Methods We use a target capture approach and the Angiosperms353 universal probes to reconstruct a robust dated phylogenetic tree for the family. This phylogenetic framework, combined with seed dispersal traits, biome data and biogeographic ranges, allows the reconstruction of the biogeographical history of the group. Results Ancestral range reconstructions suggest a Gondwanan origin (Africa/South America), with several intercontinental dispersals within the family and few transitions between biomes. Relative abundance of fruit dispersal types differed by both continent and biome. However, intercontinental colonizations were only significantly enhanced by water dispersal (drift fruit), and there was no evidence that seed dispersal modes influenced biome shifts. Main Conclusions Our analysis reveals a paradox as drift fruit greatly enhanced dispersal distances at intercontinental scale but did not affect the strong biome conservatism observed.

Nurses face unprecedented harms from the COVID-19 pandemic. A survey by AMN Healthcare found that registered nurses experienced significantly elevated levels of stress, burnout, and other challenges that led nearly 1 million to consider leaving nursing altogether. Despite the challenges, a confluence of positive factors present great confidence that the nursing profession can bounce back and become much stronger due to lessons learned and hardships overcome during the pandemic. There is near-universal awareness that solving the significant challenges to nursing is vitally important, because the health of the American people depends on the health of the nation's nurses.

International audience; Premise To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit. Methods We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76% of all genera in the order). Results Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed. Conclusions High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.

International audience; Organised by CSTB, FSF is a three-day event that fosters dialogue among scientists, academics and professionals in the field of facade fire safety. FSF 2019 promote the cooperation between manufacturers and researchers. Symposium scope & topics are: 1-Facade materials and systems behaviour in fire, 2-Facade testing and fire propagation, 3-Facade testing and assessments methods, 4-Numerical modelling and case studies, 5-Risk Management and Regulation.

International audience; Plant architecture strongly influences ecological performance, yet its role in plant evolution has been weakly explored. By testing both phylogenetic and environmental signals, it is possible to separate architectural traits into four categories: development constraints (phylogenetic signal only); convergences (environmental dependency only); key confluences to the environmental driver (both); unknown (neither).We analysed the evolutionary history of the genus Euphorbia, a model clade with both high architectural diversity and a wide environmental range. We conducted comparative analyses of 193 Euphorbia species worldwide using 73 architectural traits, a dated phylogeny, and climate data.We identified 14 architectural types in Euphorbia based on trait combinations. We found 22 traits and three types representing convergences under climate groups; 21 traits and four types showing phylogenetic signal but no relation to climate; and 16 traits and five types with both climate and phylogenetic signals. Major drivers of architectural trait evolution likely include water stress in deserts (selected for succulence, continuous branching), frost disturbance in temperate systems (selected for simple, prostrate, short‐lived shoots) and light competition (selected for arborescence). Simple architectures allowed resilience to disturbance, and frequent transitions into new forms. Complex architectures with functional specialisation developed under stable climates but have low evolvability.

Macrophages are innate immune cells that play important roles in various physiological and pathological processes. Evaluation of pro-inflammatory effects of drugs on macrophages has become commonplace in preclinical drug development prior to human clinical trials. Despite their body-wide distribution, tissue macrophages are often difficult to collect from large animals and humans in a noninvasive manner. Therefore, in vitro-differentiated macrophages are important tools to facilitate cross-species analysis of macrophage function. Although cynomolgus monkeys are an essential non-rodent species for preclinical research, in vitro differentiation of cynomolgus-monkey macrophages has been poorly characterized. In the present unit, we describe a protocol to differentiate cynomolgus-monkey macrophages from isolated bone marrow mononuclear cells (BMMCs). In contrast to monocytes, cynomolgus-monkey BMMCs show robust expansion in the presence of macrophage colony-stimulating factor in vitro, which allows expansion of many cells from a single animal donor. Macrophages differentiated from BMMCs retain many of the macrophage phenotypes and functions, including phagocytosis and cytokine release, and therefore can be used as a surrogate to assess effects of drugs on cynomolgus-monkey macrophages. © 2019 by John Wiley & Sons, Inc.

Background: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. Methods/design: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Discussion: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smearnegative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. Trial registration: International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.

Introduction Low and middle income countries bear a disproportionate burden of paediatric morbidity and mortality. South Africa, a middle income country, has unacceptably high mortality in children less than 5 years of age. Many factors that contribute to the child mortality rate are time sensitive and require efficient access to emergency care. Delays and barriers within the emergency medical services (EMS) system increase paediatric morbidity and mortality from time sensitive illnesses. Methods This study is a qualitative evaluation of the prehospital care system for paediatric patients in Cape Town, South Africa. A purposive sample of healthcare personnel within and interacting with the EMS system were interviewed. A structured interview form was used to gather data. All interviews were audio recorded and transcribed; two independent reviewers performed blinded content analysis of the transcribed script. Results 33 structured interviews were conducted over a 4 week period. Eight broad themes were identified during coding, including: access, communication, community education, equipment, infrastructure, staffing, training and triage. Subcategories were used to identify areas for targeted intervention. Overall agreement between the two independent coders was 93.36%, with a κ coefficient of 0.69. Conclusions The prehospital system is central to delivering time sensitive care for paediatric patients. In a single centre middle income setting, communication barriers between dispatch personnel and medical facilities/EMS personnel were deemed to be a high priority intervention in order to improve care delivery. Other areas for targeted interventions should include broadening the advanced life support provider base and introducing basic medical language in dispatch staff training.

Background Despite the high burden of pediatric mortality from preventable conditions in low and middle income countries and the existence of multiple tools to prioritize critically ill children in low-resource settings, no analysis exists of the reliability and validity of these tools in identifying critically ill children in these scenarios. Methods The authors performed a systematic search of the peer-reviewed literature published, for studies pertaining to for triage and IMCI in low and middle-income countries in English language, from January 01, 2000 to October 22, 2013. An updated literature search was performed on on July 1, 2015. The databases searched included the Cochrane Library, EMBASE, Medline, PubMed and Web of Science. Only studies that presented data on the reliability and validity evaluations of triage tool were included in this review. Two independent reviewers utilized a data abstraction tool to collect data on demographics, triage tool components and the reliability and validity data and summary findings for each triage tool assessed. Results Of the 4,717 studies searched, seven studies evaluating triage tools and 10 studies evaluating IMCI were included. There were wide varieties in method for assessing reliability and validity, with different settings, outcome metrics and statistical methods. Conclusions Studies evaluating triage tools for pediatric patients in low and middle income countries are scarce. Furthermore the methodology utilized in the conduct of these studies varies greatly and does not allow for the comparison of tools across study sites. Electronic supplementary material The online version of this article (doi:10.1186/s12887-017-0796-x) contains supplementary material, which is available to authorized users.

Triage Tools Data Abstraction. (PDF 126Â kb)

Systematic review inclusion and exclusion criteria. (DOCX 71Â kb)

Search Strategy. (DOCX 24Â kb)

Postoperative skin reactions are rare but serious complications. Contact dermatitis, allergic reactions, and burns had been reported. Drugs, disinfectant solutions used for skin preparation, wound dressings had associated with these skin reactions. %10 Povidone iodine solution, being a powerful antiseptic and wide spectrum disinfectant has recently replaced iodine solutions because of sensitivity reactions reported.It has a dark, amber brown color and gives the skin this color. Contact dermatitis, burns had been reported in cases who had skin preparation with %10 povidone iodine. In our case report, some postoperative skin reactions had been described, the possible causes discussed and the important points for careful preoperative skin preparation with povidone iodine had been reviewed., Ameliyat sonrası cilt reaksiyonları ender bildirilen ancak ciddi komplikasyonlardır. Kontakt dermatit, alerjik reaksiyonlar, yanık olguları bildirilmiştir. Bu cilt reaksiyonlarından ilaçlar, cilt hazırlığı için kullanılan solüsyonlar, yara pansuman malzemeleri gibi etkenler sorumlu tutulmuştur. %10 Povidon iyot solüsyonu, güçlü bir antiseptik ve geniş spektrumlu bir dezenfektan olarak, son yıllarda bildirilen sensitivite reaksiyonları nedeniyle iyot solüsyonunun yerini almıştır. Koyu amber kahverengidir ve cilde rengini verir. %10 Povidon iyot solüsyonu ile cilt temizliği uygulanan olgularda, kontakt dermatit, yanık gibi çeşitli cilt reaksiyonları bildirilmiştir. Olgu sunumumuzda, postoperatif dönemde karşılaştığımız bazı cilt reaksiyonları bildirilmiş, olası nedenleri tartışılarak, ameliyat öncesi %10 povidon iyot solüsyonu ile cilt hazırlığında özen gösterilmesi gereken noktalar belirtilmiştir.

Plague has three distinct clinical forms. Bubonic plague may resemble many viral syndromes; a distinct feature is buboes. Buboes are swollen lymph nodes filled with multiplying bacteria. They form near the bacteria’s entry point into the bloodstream. Septicemic plague symptoms can include abdominal pain and shock, with bleeding into skin and internal organs. Tissue manifestations include fingers, toes, or other areas turning black and necrotic. Bubonic and septicemic forms are transmitted by flea bites or the handling of infected animals. Pneumonic plague is easily transmitted from human to human by the inhalation of infectious droplets. Pneumonic plague is often lethal, resulting in respiratory failure and shock. Antibiotic treatment should be started as soon as plague as suspected. A vaccine, which is no longer being manufactured, was effective against the bubonic plague but not pneumonic plague. Research is ongoing for a vaccine effective against pneumonic plague, the form most likely to be utilized as a biological weapon.

Article consultable sur [http://web.b.ebscohost.com.inshs.bib.cnrs.fr/ehost/detail/detail?vid=0&sid=4978745d-4866-47ef-84fe-c9bf232b3b92%40sessionmgr120&bdata=Jmxhbmc9ZnImc2l0ZT1laG9zdC1saXZl#AN=118170097&db=asn]; International audience; This article addresses the characterization of resistive archaeological targets and near surface structures by electromagnetic induction (EMI). It presents tests achieved with the DualEM-421S instrument (Dualem Inc., Milton, Canada) in order to be able to quantitatively compare these measurements to the standard technique of direct-current (d.c.) resistivity. The test was done over the Gallo-roman site of Vieil-Evreux in Normandy, France and one-dimensional (1D) and three-dimensional (3D) inversions were applied to the data set obtained. We have first investigated the signal-to-noise ratio of each of the six DualEM receiver coils both in a static mode and for a quad-pulled system. The dependence on the roll angle was also measured and it is shown that rotation of DualEM must be taken into account if the roll angle is more than ±10°. Absolute calibration and in-phase/quadrature (out of phase) component discrimination was checked by measuring the response of a small conductive and non-magnetic sphere. Several electromagnetic soundings by measuring the instrument response at different heights were done in order to check the quadrature (out-of-phase) response of the instrument. Inversions of these electromagnetic soundings were compared to d.c. vertical electric soundings (VESs) over four locations and found in accordance. Several maps using different coil configurations (HCP, VCP, PERP) and different heights were performed and inverted, both for a wide mesh (5 m) and for a finer one (0.5 m). The wide mesh allows a global and rapid description of the surface geology context (continuous d.c. measurements cannot deliver equivalent depth of investigation). The fine mesh conductivity maps clearly show the walls of a fanum (temple) as well as other structures and prove that the DualEM-421S is able to map correctly archaeological resistive targets. These maps and their interpretations were compared to previous results obtained by d.c. technique.

Phosphorylation of histone H3 protein at serine 10 is an important step in chromatin remodeling during transcriptional transactivation. IkappaB kinase-alpha (IKK-alpha) and Mitogen- and Stress-activated protein Kinases 1 and 2 (MSK1/2) have been shown to play key roles in the transcriptional regulation of immediate early genes such as c-fos. Interestingly, IKK-alpha and MSK1/2 have also been implicated as histone H3-Ser10 kinases. In this work, we have shown that MSK1/2 are required for epidermal growth factor (EGF)-induced, but not tumor necrosis factor-induced, histone H3-Ser10 phosphorylation, both globally and at specific promoters. Consistent with this, MSK1/2 are required for optimal immediate early c-fos transcription in response to EGF potentially through control of both H3-Ser10 and promoter-associated cAMP-response element-binding protein phosphorylation. Furthermore, MSK1/2 control EGF-induced IkappaB alpha promoter H3-Ser10 phosphorylation in the absence of elevated transcription. These studies demonstrate the existence of pathway-specific mechanisms to control histone H3-Ser10 phosphorylation and gene expression.

Mitogenic activation of expression of immediate-early genes, such as c-fos, is controlled through signal-induced phosphorylation of constitutively bound transcription factors that is correlated with a nucleosomal response that involves inducible chromatin modifications, such as histone phosphorylation and acetylation. Here we have explored a potential role for the transcription factor NF-kappaB and its associated signaling components in mediating induction of c-fos gene expression downstream of epidermal growth factor (EGF)-dependent signaling. Here we show that EGF treatment of quiescent fibroblast does not induce the classical pathway of NF-kappaB activation through IkappaB kinase (IKK)-directed IkappaBalpha phosphorylation. Interestingly, efficient induction of c-fos transcription requires IKKalpha, one of the subunits of the IkappaB kinase complex. The NF-kappaB subunit, p65/RelA, is found constitutively associated with the c-fos promoter, and knock-out of this transcription factor significantly reduces c-fos gene expression. Importantly, EGF induces the recruitment of IKKalpha to the c-fos promoter to regulate promoter-specific histone H3 Ser(10) phosphorylation in a manner that is independent of p65/RelA. Collectively, our data demonstrate that IKKalpha and p65/RelA contribute significantly to EGF-induced c-fos gene expression in a manner independent of the classical, IkappaBalpha degradation, p65/RelA nuclear accumulation response pathway.

Extensive data indicate that the transcription factor NF kappa B is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)-ABL. Consistent with this, evidence has been presented that NF kappa B activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NF kappa B-dependent gene expression or whether they may augment or interfere with other stimuli that activate NF kappa B. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NF kappa B. This suppression of NF kappa B is manifested by an inhibition of TNF-induced inhibitor of NF kappa B (IKK) activity and NF kappa B DNA binding potential but not by blocking TNF-induced nuclear accumulation of NF kappa B/p65. The inhibition of NF kappa B is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NF kappa B-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCR-ABL to activate NF kappa B involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

IntroductionThe goal of an Emergency Medical Services (EMS) system is to prevent needless death or disability from time-sensitive disease processes. Despite growing evidence that these processes contribute significantly to mortality in low- and middle- income countries (LMICs), there has been little focus on the development of EMS systems in poor countries.ProblemThe objective of this study was to understand the utilization pattern of a newly-implemented EMS system in Ruhiira, Uganda.MethodsAn EMS system based on community priorities was implemented in rural Uganda in 2009. Six months of ambulance logs were reviewed. Patient, transfer, and clinical data were extracted and analyzed.ResultsIn total, 207 cases were reviewed. Out of all transfers, 66% were for chief complaints that were obstetric related, while 12% were related to malaria. Out of all activations, 77.8% were for female patients. Among men, 34% and 28% were related to malaria and trauma, respectively. The majority of emergency transfers were from district to regional hospitals, including 52% of all obstetric transfers, 65% of malaria transfers, and 62% of all trauma transfers. There was no significant difference in the call to arrival on scene time, the time to scene or the scene to treatment time during the day and night (P > .05). Cost-benefit analysis revealed a cost of $89.95 per life saved with an estimated $0.93/capita to establish the system and $0.09/capita/year to maintain the system.ConclusionContrary to current belief, EMS systems in rural Africa can be affordable and highly utilized, particularly for life-threatening, nontrauma complaints. Construction of a simple but effective EMS system is feasible, acceptable, and an essential component to the primary health care system of LMICs.Stewart De RamirezS, DollJ, CarleS, AnestT, AriiM, HsiehYH, OkongoM, MoreskyR, SachsSE, MillinM. Emergency response in resource poor-settings: a review of a newly-implemented EMS system in rural Uganda. Prehosp Disaster Med. 2014;29(3):1-6.

Bcl-3 is a distinctive member of the IkappaB family of NF-kappaB inhibitors because it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due to its location at a breakpoint junction in some cases of human B-cell chronic lymphocytic leukemia and that it is highly expressed in human breast tumor tissue. To analyze the effects of Bcl-3 dysregulation in breast epithelial cells, we created stable immortalized human breast epithelial cell lines either expressing Bcl-3 or carrying the corresponding vector control plasmid. Analysis of the Bcl-3-expressing cells suggests that these cells have a shortened G(1) phase of the cell cycle as well as a significant increase in hyperphosphorylation of the retinoblastoma protein. Additionally, the cyclin D1 gene was found to be highly expressed in these cells. Upon further analysis, Bcl-3, acting as a coactivator with NF-kappaB p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF-kappaB binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G(1) transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.

Wnt-4 signaling plays a critical role in kidney development and is associated with the epithelial conversion of the metanephric mesenchyme. Furthermore, secreted Frizzled-related proteins (sFRPs) that can bind Wnts are normally expressed in the developing metanephros, and function in other systems as modulators of Wnt signaling. sfrp-1 is distributed throughout the medullary and cortical stroma in the metanephros, but is absent from condensed mesenchyme and primitive tubular epithelia of the developing nephron where wnt-4 is highly expressed. In contrast, sfrp-2 is expressed in primitive tubules. To determine their role in kidney development, recombinant sFRP-1, sFRP-2 or combinations of both were applied to cultures of 13-dpc rat metanephroi. Both tubule formation and bud branching were markedly inhibited by sFRP-1, but concurrent sFRP-2 treatment restored some tubular differentiation and bud branching. sFRP-2 itself showed no effect on cultures of metanephroi. In cultures of isolated, induced rat metanephric mesenchymes, sFRP-1 blocked events associated with epithelial conversion (tubulogenesis and expression of lim-1, sfrp-2 and E-cadherin); however, it had no demonstrable effect on early events (compaction of mesenchyme and expression of wt1). As shown herein, sFRP-1 binds Wnt-4 with considerable avidity and inhibits the DNA-binding activity of TCF, an effector of Wnt signaling, while sFRP-2 had no effect on TCF activation. These observations suggest that sFRP-1 and sFRP-2 compete locally to regulate Wnt signaling during renal organogenesis. The antagonistic effect of sFRP-1 may be important either in preventing inappropriate development within differentiated areas of the medulla or in maintaining a population of cortical blastemal cells to facilitate further renal expansion. On the other hand, sFRP-2 might promote tubule formation by permitting Wnt-4 signaling in the presence of sFRP-1.

Cet ouvrage a obtenu le label de la "Convention sur la diversité biologique".; Cet ouvrage qui réunit des contributions de personnalités scientifiques, économistes, dirigeants et gestionnaires, aborde à travers différentes entrées les deux questions suivantes : - Comment concilier activités économiques et biodiversité ? - Est-il aujourd'hui possible de faire de la gestion de la biodiversité un atout ? Au-delà de la simple sensibilisation à la biodiversité, ce guide apporte des éclairages quant aux enjeux qu'il convient de considérer, aux approches de gestion de la biodiversité à l'échelle d'un produit mais aussi d'un territoire, ainsi qu'à certaines avancées prospectives évoquées au sein d'ORÉE (intégration de la biodiversité dans la comptabilité des organisations, complexité des interactions dynamiques entre systèmes humains et systèmes vivants). Plus d'une quinzaine d'études de cas conduites par des structures adhérentes et partenaires ont été recueillies afin d'illustrer concrètement les diverses manières de concilier les enjeux de biodiversité et ceux des activités économiques dans le contexte actuel. [Extrait du résumé de l'éditeur].

A shifting of reality, rites and rhythm, cultural continuity : an approach to new beliefs through the carnival in Greece. The ethnological approach to a carnival in a Greek village in Thessalonica leads us to put forward an anthropological hypothesis about an invariant element which is rhythm and its role in the phenomenon of cultural continuity. This time-space opening offered by the carnival permits one to take into account the realities and disorders of the present-day world through the representation of new subversions and threats treated in a symbolical logic which remains permanent : the creation of new beliefs. Rhythm seems to be a binding force specific to the culture, a sub-stance of the "religere" ; supporting the symbolical process between order and disorder in the understanding of reality ; it seems to be the guarantee of cultural continuity and of an identity which lives on and recreates itself., L'approche ethnologique d'un carnaval, dans un village grec de Thessalie, nous amène à poser une hypothèse anthropologique sur un invariant, le rythme, et son rôle dans le phénomène de la continuité culturelle. Cet espace-temps d'ouverture du carnaval permet la prise en charge du changement d'une réalité et des désordres du monde actuel, par la représentation des subversions et des menaces nouvelles traitées dans une logique symbolique qui reste permanente ; nous assistons à la genèse de nouvelles croyances. Le rythme apparaît comme un liant propre à la culture, une substance du "religere" ; soutenant l'opération symbolique entre ordre et désordre dans l'appréhension de la réalité, il semble constituer le garant de la continuité culturelle et d'une identité qui se maintient et se recrée., Anest Marie-christine. Mouvances du réel, rites et rythme, continuité culturelle : Approche de nouvelles croyances à travers le carnaval en Grèce. In: Cahiers de sociologie économique et culturelle, n°21, 1994. pp. 9-21.

Small RNAs targeted to gene promoters in human cells can mediate transcriptional gene silencing (TGS) by directing silent state epigenetic modifications to targeted loci. Many mechanistic details of this process remain poorly defined, and the ability to stably modulate gene expression in this manner has not been explored. Here we describe the mechanisms of establishment and maintenance of long-term transcriptional silencing of the human ubiquitin C gene (UbC). Sustained targeting of the UbC promoter with a small RNA for a minimum of 3 days resulted in long-term silencing which correlated with an early increase in histone methylation and a later increase in DNA methylation at the targeted locus. Transcriptional silencing of UbC required the presence of a promoter-associated RNA. The establishment and maintenance of the TGS were shown to require distinct protein factors. Argonaute 1 (Ago1), DNA methyltransferase 3a (DNMT3a) and histone deacetylase 1 (HDAC1) were required for the initiation of silencing, and DNA methyltransferase 1 (DNMT1) was necessary for maintenance. Taken together the data presented here highlight the cellular pathway with which noncoding RNAs interact to epigenetically regulate gene expression in human cells.

Phosphorylation of histone H3 protein at serine 10 is an important step in chromatin remodeling during transcriptional transactivation. I[kappa]B kinase-[alpha] (IKK-[alpha]) and Mitogen- and Stress-activated protein Kinases 1 and 2 (MSK1/2) have been shown to play key roles in the transcriptional regulation of immediate early genes such as c-fos. Interestingly, IKK-[alpha] and MSK1/2 have also been implicated as histone H3-Ser¹⁰ kinases. In this work, we have shown that MSK1/2 are required for epidermal growth factor (EGF)-induced, but not tumor necrosis factor-induced, histone H3-Ser¹⁰ phosphorylation, both globally and at specific promoters. Consistent with this, MSK1/2 are required for optimal immediate early c-fos transcription in response to EGF potentially through control of both H3-Ser¹⁰ and promoter-associated cAMP-response element-binding protein phosphorylation. Furthermore, MSK1/2 control EGF-induced I[kappa]B[alpha] promoter H3-Ser¹⁰ phosphorylation in the absence of elevated transcription. These studies demonstrate the existence of pathway-specific mechanisms to control histone H3-Ser¹⁰ phosphorylation and gene expression.

Mitogenic activation of expression of immediate-early genes, such as c-fos, is controlled through signal-induced phosphorylation of constitutively bound transcription factors that is correlated with a nucleosomal response that involves inducible chromatin modifications, such as histone phosphorylation and acetylation. Here we have explored a potential role for the transcription factor NF-kappaB and its associated signaling components in mediating induction of c-fos gene expression downstream of epidermal growth factor (EGF)-dependent signaling. Here we show that EGF treatment of quiescent fibroblast does not induce the classical pathway of NF-kappaB activation through IkappaB kinase (IKK)-directed IkappaBalpha phosphorylation. Interestingly, efficient induction of c-fos transcription requires IKKalpha, one of the subunits of the IkappaB kinase complex. The NF-kappaB subunit, p65/RelA, is found constitutively associated with the c-fos promoter, and knock-out of this transcription factor significantly reduces c-fos gene expression. Importantly, EGF induces the recruitment of IKKalpha to the c-fos promoter to regulate promoter-specific histone H3 Ser(10) phosphorylation in a manner that is independent of p65/RelA. Collectively, our data demonstrate that IKKalpha and p65/RelA contribute significantly to EGF-induced c-fos gene expression in a manner independent of the classical, IkappaBalpha degradation, p65/RelA nuclear accumulation response pathway.

Mitogenic activation of expression of immediate-early genes, such as c-fos, is controlled through signal-induced phosphorylation of constitutively bound transcription factors that is correlated with a nucleosomal response that involves inducible chromatin modifications, such as histone phosphorylation and acetylation. Here we have explored a potential role for the transcription factor NF-kappaB and its associated signaling components in mediating induction of c-fos gene expression downstream of epidermal growth factor (EGF)-dependent signaling. Here we show that EGF treatment of quiescent fibroblast does not induce the classical pathway of NF-kappaB activation through IkappaB kinase (IKK)-directed IkappaBalpha phosphorylation. Interestingly, efficient induction of c-fos transcription requires IKKalpha, one of the subunits of the IkappaB kinase complex. The NF-kappaB subunit, p65/RelA, is found constitutively associated with the c-fos promoter, and knock-out of this transcription factor significantly reduces c-fos gene expression. Importantly, EGF induces the recruitment of IKKalpha to the c-fos promoter to regulate promoter-specific histone H3 Ser(10) phosphorylation in a manner that is independent of p65/RelA. Collectively, our data demonstrate that IKKalpha and p65/RelA contribute significantly to EGF-induced c-fos gene expression in a manner independent of the classical, IkappaBalpha degradation, p65/RelA nuclear accumulation response pathway.

NF-κB is a principal transcriptional regulator of diverse cytokine-mediated processes and is tightly controlled by the IκB kinase complex (IKK-α/β/γ). IKK-β and IKK-γ are critical for cytokine-induced NF-κB function, whereas IKK-α is thought to be involved in other regulatory pathways1,2,3,4. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment1,5,6,7. Here we demonstrate nuclear accumulation of IKK-α after cytokine exposure, suggesting a nuclear function for this protein. Consistent with this, chromatin immunoprecipitation (ChIP) assays reveal that IKK-α was recruited to the promoter regions of NF-κB-regulated genes on stimulation with tumour-necrosis factor-α. Notably, NF-κB-regulated gene expression is suppressed by the loss of IKK-α and this correlates with a complete loss of gene-specific phosphorylation of histone H3 on serine 10, a modification previously associated with positive gene expression. Furthermore, we show that IKK-α can directly phosphorylate histone H3 in vitro, suggesting a new substrate for this kinase. We propose that IKK-α is an essential regulator of NF-κB-dependent gene expression through control of promoter-associated histone phosphorylation after cytokine exposure. These findings provide additional insight into the role of the IKK complex in NF-κB-regulated gene expression.

Extensive data indicate that the transcription factor NFκB is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)ABL. Consistent with this, evidence has been presented that NFκB activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NFκB-dependent gene expression or whether they may augment or interfere with other stimuli that activate NFκB. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NFκB. This suppression of NFκB is manifested by an inhibition of TNF-induced inhibitor of NFκB (IKK) activity and NFκB DNA binding potential but not by blocking TNF-induced nuclear accumulation of NFκB/p65. The inhibition of NFκB is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NFκB-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCRABL to activate NFκB involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

Bcl-3 is a distinctive member of the IκB family of NF-κB inhibitors because it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due to its location at a breakpoint junction in some cases of human B-cell chronic lymphocytic leukemia and that it is highly expressed in human breast tumor tissue. To analyze the effects of Bcl-3 dysregulation in breast epithelial cells, we created stable immortalized human breast epithelial cell lines either expressing Bcl-3 or carrying the corresponding vector control plasmid. Analysis of the Bcl-3-expressing cells suggests that these cells have a shortened G1 phase of the cell cycle as well as a significant increase in hyperphosphorylation of the retinoblastoma protein. Additionally, the cyclin D1 gene was found to be highly expressed in these cells. Upon further analysis, Bcl-3, acting as a coactivator with NF-κB p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF-κB binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G1 transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.

Secreted Frizzled-related protein-1 (sFRP-1) contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzleds. To facilitate the biochemical and biological analysis of sFRP-1, we developed a mammalian recombinant expression system that yields approximately 3 mg of purified protein/liter of conditioned medium. Using this recombinant protein, we demonstrated that sFRP-1 and Wg (wingless) interact in enzyme-linked immunosorbent and co-precipitation assays. Surprisingly, a derivative lacking the cysteine-rich domain retained the ability to bind Wg. Cross-linking experiments performed with radioiodinated sFRP-1 provided definitive evidence that sFRP-1 and Wg bind directly to each other. Besides detecting a cross-linked complex consistent in size with 1:1 stoichiometry of sFRP-1 and Wg, we also observed a larger complex whose size suggested the presence of a second sFRP-1 molecule. The formation of both complexes was markedly enhanced by an optimal concentration of exogenous heparin, emphasizing the potential importance of heparan-sulfate proteoglycan in Wnt binding and signaling. sFRP-1 exerted a biphasic effect on Wg activity in an armadillo stabilization assay, increasing armadillo level at low concentrations but reducing it at higher concentrations. These results provide new insights about the Wnt binding and biological activity of sFRPs.

Recently, the isolation of presumptive diazotrophic endophytic bacteria from rice seedlings has been reported (Ladha et al. 1997; Yanni et al. 1996, 1997). These microbes were detected after the roots had been surface sterilised and the plant tissue macerated, diluted and the suspensions plated out for viable colony-forming bacteria to determine the most probable number (MPN). Based on these results, it was suggested that the detected rhizobia had formed a potential endophytic association within the roots of rice plants grown in fields rotated with Egyptian berseem clovers (Yanni et al. 1996). The rhizobia were identified as Rhizobium leguminosarum bv. trifolii strains and we have compared the biological properties of several of these strains with the archetypal R. l. bv. trifolii strain, ANU843.

The writer describes the making of loaves of bread in Cyprus for the Christmas and New Year celebrations, showing the different stages. But beyond the ethnographic relation, we are led to see the symbolic character of this production. As a matter of fact, there is an analogy between the making of the bread and reproduction of life. The choice of the Christmas and New Year period, which is the time of transition and of a mythical birth throws some light on a ritual which signifies the domestic re-creation of the world., L'auteur décrit la confection des pains de fête à Chypre dont elle montre les différentes étapes. Mais au-delà de la relation ethnographique, nous sommes conduits à saisir le caractère symbolique de cette production. Il existe en effet une analogie entre la fabrication du pain et la reproduction de la vie. Le choix de la période de Noël-Jour de l’An, temps du passage et de la naissance mythique, éclaire un rituel qui signifie la recréation domestique du monde., Anest Marie-christine. La confection des pains de la période Noël-Jour de l'An à Chypre. La recréation domestique du monde. In: Cahiers de sociologie économique et culturelle, n°24, 1995. pp. 33-47.

Marie-Christine Anest Couffin, Mythical Time and the Egg in the Greek popular calendar The ritual use of the egg in the Greek holiday calendar is associated with the cyclical dimension of a highly-charged-sense of time. The festive days of Spring represent the tradition between the Winter and Summer seasons and symbolize the abolition of time and regeneration. Socially, it is the time of the regeneration of the individual and of the group. In this calendar-time-space, the egg plays a fundamental role in symbolizing the passage from one state to another., Anest-Couffin Marie-Christine. L'œuf dans le calendrier populaire grec et le temps mythique . In: L'Homme et la société, N. 111-112, 1994. Générations et mémoires. pp. 175-182.