Ein Gespräch : ebbes Rars über die Kuhpokken mit eignen Ohren gehört

von Herz Amschel Ahimaaz, dem Baumeister

Llibres facil de comptes fets : ab lo qual se pot traurer tota especie de comptes de tota moneda, per enter, ò trencat, tenint present los exemples que à est fi se han anyadit : recopilació de las obras de Fr. Barreme ... : obra utilisima à tot oficial de thesorería, empressaris, negociants y pagesos, encara que no sapian lo art de arismetica

Mode of access: Internet.

Análise morfológica e citogenética de medula óssea em pacientes com síndrome mielodisplásica primária

A síndrome mielodisplásica primária (SMD) compreende um grupo de doenças hematopoéticas clonal de célula tronco pluripotente cacacterizada por vários graus de pancitopenia e alterações morfológica das células hematopoeticas e risco aumentado de transformação para leucemia mielóide aguda. A citogenética e a morfologia da medula óssea desempenham um papel fundamental para o diagnóstico e o prognóstico desses pacientes. Alterações cromossômicas são encontradas em aproximadamente 30-50% dos casos. Devido à importância da análise desses fatores para escolha terapêutica, torna-se necessário definir as alterações morfológicas e citogenéticas que possam contribuir para o prognóstico. Esse trabalho visa correlacionar as características morfológicas e citogenéticas da medula óssea em pacientes com SMD primária com as classificações OMS e FAB e com o IPSS. Foram estudados 32 pacientes com SMD primária diagnosticados entre 2000 e 2009 no HUPE-UERJ. As características clínicas foram analisadas através do levantamento de prontuários. A análise citogenética foi feita pela técnica de bandeamento GTG em células da medula ossea. A análise morfológica da biópsia de medula óssea e do mielograma foram realizadas através da revisão de lâminas. Vinte e três pacientes foram classificados em estágios iniciais da doença (22 AR, 1 ARSA) e 9 em estágio avançado AREB de acordo com a FAB. Alterações cromossômicas foram detectadas em 16 pacientes (50%). As mais frequentes foram: del(11)(q23) e del(17p). Dos pacientes com doença avançada, seis (66%) apresentaram aumento significativo da relação M:E (p=0,003) e sete (77%) possuíam alterações arquiteturais acentuadas (p<0,001) em comparação ao grupo de doença inicial. Pacientes classificados como intermediário 2 e alto risco pelo IPSS tiveram importante perda arquitetural (p<0,001), número significativamente maior de micromegacariócitos (p=0,017) e seis (85%) sofreram transformação leucêmica (p=0,006). ALIP foi significantemente aumentada nos pacientes de pior prognóstico (p=0,0 1) e naqueles com doença avançada (p=0,001). Nossos resultados apresentaram implicações potenciais para o diagnóstico e o prognóstico da SMD primária. As alterações morfológicas foram associadas com as classificações FAB, OMS e com os grupos de risco segundo o IPSS.

Differences in growth and nitrogen productivity between a stay-green genotype and a wild-type of Lolium perenne under limiting relative addition rates of nitrate supply

James Macduff, Neil Raistrick and Mervyn Humphreys (2002). Differences in growth and nitrogen productivity between a stay-green genotype and a wild-type of Lolium perenne under limiting relative addition rates of nitrate supply. Physiologia Plantarum, 116 (1), 52-61. Sponsorship: BBSRC RAE2008

The consequences of child-parent violence reflected in a life story

A process of social transformation allied with ongoing changes to the family has made possible the existence of a relatively little-known phenomenon: that of child-parent violence, which is raised as one of the most commonly experienced forms of violence in the family environment. Based on the study of this phenomenon, in our research we have used the qualitative technique of a life story, making use of a field diary in which we have taken notes on our daily work in the therapeutic context, for the purposes of mitigating the effects of such a process. The following research objectives were set: establishing the connection existing between family education style and the use of violence by the minor; and evaluating the extent to which family therapy mitigates the use of violence by the minor. The family education model, together with other dimensions, results in situations of child-parent violence occurring repeatedly, with continuing negative reinforcement from both parties in order to maintain a recurrent cycle of conduct, from which it is difficult to «escape» other than through a process of ongoing psychological therapy.

Scientifi c discourses on chronic pain without organic cause Incorporating gender perspective for pain resignifyng-repoliticizing

Chronic pain, without any organic or physical cause (DC), which in psycho-medical terminology is known as fi bromyalgia, (FM), is diagnosed each year to a considerable number of women in capitalistic societies. Our main interest in the following paper is to go in depth in the elaboration of this symptom, its treatment and the psychosocial effects, both in the social order as well as in the lives of the people who suffer from it. Our main goal in the following paper is to look deeper in the elaboration (conceptualization) of this symptom, its treatment and psychological affects, both in the social order as well as in the lives of the people who suffer from it, we are using linked speeches in Spanish magazines publications. The result has been the emergence of three hegemonic discourse positions: One position “scientist”, one “therapeutic of the conformity” position and one “economic and legalistic” position. Each of these has a specifi c feature, but on the whole, is enhanced, producing effects such as the absence of social context to explain the disease; disregard of gender differences in the management and treatment; the instrumentalization of pain to legitimize their practices and the subjection of women to the “psycho-biomedical” paradigm. In that way, a new signifi cance and politicization of the concept of pain is proposed.

Alien gosd in the new epics: Noah remythologised through the ancient astronaut hypothesis in Abel's Montagut's "La gesta d'Utnoa"

Modern scientific world-view has undermined traditional myths, the functional survival of which seems to depend today in the West on a positivist justification. This would place them in the field of real History, through their study and revitalization by pseudoscientific disciplines such as the Atlantis and the ancient astronaut hypotheses. These have inspired new epic poems in (regular) verse that combine classic and/or biblical myths with a (pseudo)scientific modern world-view. For example, the critical rewriting of Noah’s myth by using the ancient astronaut hypothesis as a fictional device to produce a contemporary kind of plausibility allowed Abel Montagut to renew epic poetry, updating it also by adopting science fiction chronotopes in order to structure his fictional construction and to generate a high ethical sense for our time. Thus, his Poemo de Utnoa (1993) / La gesta d’Utnoa (1996), which has become a major classic of the literature in Esperanto thanks to its original version in this language, is a landmark of both science fiction and neo-biblical epics. This poem is written from a secular and purely literary perspective.

Spontaneous intramedullary apoptosis is present in disorders other than myelodysplasia

Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders characterized by peripheral cytopenias in the presence of normo- or hypercellular dysplastic marrow. It has been suggested that premature intramedullary apoptosis may contribute to this phenomenon. We used terminal dUTP nick-end labeling (TUNEL) of bone marrow biopsy specimens and cytocentrifuge preparations from patients with MDS and a variety of other hematopoietic disorders to determine whether there is increased intramedullary apoptosis in MDS and whether any such effect is specific to MDS. TUNEL labeling of bone marrow from 24 patients with MDS revealed significant positivity in 10 of 11 patients with refractory anemia (RA), five of seven with RA and excess of blasts (RAEB), all three patients with RAEB in transformation (RAEB-t), and all three patients with RA with ring sideroblasts (RARS). The percent of positive cells ranged from 5 to 50% but showed no apparent correlation with morphological subtype. In a series of 29 patients with acute leukemia, 17 showed significant positivity (13 of 13 with myeloid disease: three M1, seven M2, one M3, two M4; four of 16 patients with lymphoid disease: one Burkitt-type lymphoma, two null acute leukemia, and one common acute lymphoid leukemia). Intramedullary apoptosis was associated with myeloid or early committed progenitor cells and was highest in secondary acute myeloid leukemia (AML). Normal bone marrow samples from 12 individuals showed no evidence of apoptosis. Our results suggest that an increased level of intramedullary apoptosis is apparent in both patients with MDS and those with AML; those with secondary AML have the highest levels. The relative absence of such findings in lymphoid malignancy suggests that the apoptotic pathways are different in this lineage.

Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells

The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34 + cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript andor exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicingprocessing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expressionsplicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34 + cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processespathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified.

Identification of novel retinoid receptors and their roles in vertebrate and invertebrate nervous systems

In vertebrates, signaling by retinoic acid (RA) is known to play an important role in embryonic development, as well as organ homeostasis in the adult. In organisms such as adult axolotls and newts, RA is also important for regeneration of the CNS, limb, tail, and many other organ systems. RA mediates many of its effects in development and regeneration through nuclear receptors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs). This study provides evidence for an important role of the RA receptor, RAR~2, in ,( '. regeneration ofthe spinal cord and tail of the adult newt. It has previously been proposed that the ability of the nervous system to regenerate might depend on the presence or absence of this RAR~2 isoform. Here, I show for the very first time, that the regenerating spinal cord of the adult newt expresses this ~2 receptor isoform, and inhibition of retinoid signaling through this specific receptor with a selective antagonist inhibits tail and spinal cord regeneration. This provides the first evidence for a role of this receptor in this process. Another species capable of CNS ~~generation in the adult is the invertebrate, " Lymnaea stagnalis. Although RA has been detected in a small number of invertebrates (including Lymnaea), the existence and functional roles of the retinoid receptors in most invertebrate non-chordates, have not been previously studied. It has been widely believed, however, that invertebrate non-chordates only possess the RXR class of retinoid receptors, but not the RARs. In this study, a full-length RXR cDNA has been cloned, which was the first retinoid receptor to be discovered in Lymnaea. I then went on to clone the very first full-length RAR eDNA from any non-chordate, invertebrate species. The functional role of these receptors was examined, and it was shown that normal molluscan development was altered, to varying degrees, by the presence of various RXR and RAR agonists or antagonists. The resulting disruptions in embryogenesis ranged from eye and shell defects, to complete lysis of the early embryo. These studies strongly suggest an important role for both the RXR and RAR in non-chordate development. The molluscan RXR and RAR were also shown to be expressed in the adult, nonregenerating eNS, as well as in individual motor neurons regenerating in culture. More specifically, their expression displayed a non-nuclear distfibution, suggesting a possible non-genomic role for these 'nuclear' receptors. It was shown that immunoreactivity for the RXR was present in almost all regenerating growth cones, and (together with N. Farrar) it was shown that this RXR played a novel, non-genomic role in mediating growth cone turning toward retinoic acid. Immunoreactivity for the novel invertebrate RAR was also found in the regenerating growth cones, but future work will be required to determine its functional role in nerve cell regeneration. Taken together, these data provide evidence for the importance of these novel '. retinoid receptors in development and regeneration, particularly in the adult nervous system, and the conservation of their effects in mediating RA signaling from invertebrates to vertebrates.

Identification and characterization of retinoic acid-induced morphological and electrophysiological changes in an invertebrate nervous system

The vitamin A metabolite, retinoic acid (RA) is known to play an important role in the development, patterning and regeneration of nervous tissue, both in the embryo and in the adult. Classically, RA is known to mediate the transcription of target genes through the binding and activation ofits nuclear receptors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Recently, mounting evidence from many animal models has implicated a number of RA-mediated effects operating independently of gene transcription, and thus highlights nove~ nongenornic actions of RA. For example, recent work utilizing cultured neurons from the pond snaa Lymnaea stagnalis, has shown that RA can elicit a regenerative response, growth cone turning, independently of "classical" transcriptional activation While this work illustrates a novel regeneration-inducing effect in culture, it is currently -unknown whether RA also induces regeneration in situ. This study has sought to determine RA's regenerative effucts at the morphological and molecular levels by utilizing an in situ approach focusing on a single identified dopaminergic neuron which possesses a known "mapped" morphology within the CNS. These studies show, for the first time in an invertebrate, that RA can increase neurite outgrowth of dopaminergic cells that have undergone a nerve-crush injury. Utilizing Western blot analysis, it was shown that this effect appears to be independent of any changes in whole CNS expression levels of either the RAR or RXR. Additionally, utilizing immunohistochemistry, to examine protein localization, there does not appear to be any obvious changes in the RXR expression level at the crush site. Changes in cell morphology such as neurity extension are known to be modulated by changes in neuronal firing activity. It has been previously shown that exposure to RA over many days can lead to changes in the electrophysiological properties of cultured Lymnaea neurons; however, no studies have investigated whether short-term exposure to RA can elicit electrophysiological changes and/or changes in firing pattern of neurons in Lymnaea or any other species. The studies performed here show, for the first time in any species, that short-tenn treatment with RA can elicit significant changes in the firing properties of both identified dopaminergic neurons and peptidergic neurons. This effect appears to be independent of protein synthesis, activation of protein kinase A or phospholipase C, and calcium influx but is both dose-dependent and isomer-dependent. These studies provide evidence that the RXR, but not RAR, may be involved, and that intracellular calcium concentrations decrease upon RAexposure with a time course, dose-dependency and isomer-dependency that coincide with the RA-induced electrophysiological changes. Taken together, these studies provide important evidence highlighting RA as a multifunctional molecule, inducing morphological, molecular and electrophysiological changes within the CNS, and highlight the many pathways through which RA may operate to elicit its effects.

Rôle de la synthèse de l'acide rétinoïque dans le contrôle de la prolifération et de la différenciation des cellules épithéliales mammaires

L’acide rétinoïque (AR) est le ligand des récepteurs nucléaires RAR et RXR qui agissent comme facteurs de transcription ligand-inductibles et médient ses effets biologiques. Il est connu que l’AR a des propriétés prodifférenciatrices et antiprolifératives, notamment sur les cellules de l’épithélium mammaire. Une perte de sensibilité de l’AR a toutefois été mise en évidence dans plusieurs lignées cellulaires mammaires cancéreuses, ce qui pourrait faciliter la croissance des tumeurs. Or jusqu’ici cette perte de sensibilité avait été attribuée à des défauts de la voie de signalisation de l’AR, causée par la perte de l’expression des récepteurs à l’AR dans la tumeur, bien que plusieurs lignées de cellules cancéreuses y soient tout de même très sensibles. Peu d’études se sont intéressées au rôle de la voie de synthèse de l’AR dans la transformation des cellules mammaires. En effet, l’AR est synthétisé à partir de la vitamine A, ou rétinol, son précurseur sanguin provenant de la diète. Les cellules de l’épithélium mammaire normales ont la capacité de synthétiser l’AR à partir du rétinol. Nos rapportons pour la première fois que l’épithélium mammaire est probablement le siège de la synthèse et de la signalisation de l’AR. Cela est dû, au moins en partie, à l’expression d’une enzyme de synthèse de l’AR, RALDH3, dans l’épithélium mammaire normal. Dans cette étude, nous démontrons que les cellules cancéreuses de type luminal, qui ont sensibles à l’AR (et qui expriment le récepteur des estrogènes ER, catégorie qui regroupe 75 % des tumeurs diagnostiquées) n’ont au contraire pas la capacité de sythétiser l’AR, probablement en raison d’une faible expression de RALDH3 dans les tumeurs, sous l’effet des estrogènes. Cela pourrait représenter un nouveau mécanisme favorisant la croissance des tumeurs luminales dont les cellules proliférent en présence du rétinol sanguin. RALDH1, une autre enzyme de la voie de synthèse de l’AR, et qui partage 70 % d’identité de séquence avec RALDH3, est un marqueur de tumeurs plus agressives et de la formation de métastase. Nous montrons au contraire, que RALDH3 est un marqueur d’une moindre probabilité de développer des métastases chez les patientes atteintes d’une tumeur luminale. Cela suggère des rôles different pour ces deux enzymes dans la glande mammaire. Nos résultats indiquent que RALDH1 et 3 ont des propriétés enzymatiques très différentes, ce qui est en accord avec cette dernière hypothèse. Nos données suggèrent aussi que RALDH1 et 3 pourraient être des marqueurs de populations distinctes de cellules dans la glande mammaire normale. Nous proposons d’exploiter les diffèrences entre RALDH1 et 3 afin de mettre au point des méthodes de séparation des différentes population de cellules de l’épithélium mammaire ce qui pourrait aider à comprendre le rôle de la synthèse d’AR dans ce tissu.

La Biblioteca de Catalunya: una difusió del patrimoni amb visió de futur

Màster Oficial en Estudis Avançats en Història de l'Art. Curs: 2008-2009. Directora: Imma Socias