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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.

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.