Molecular evolution in protobiological systems Final report, Dec. 1, 1961 - Nov. 30, 1964

Arc discharge of irradiated mixtures of simple organic and inorganic compounds for development of theory of molecular evolution in protobiological system

Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring

Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal–maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.Fil: Freitag, Nancy. Medicine University of Berlin; AlemaniaFil: Zwier, M. V.. University of Groningen; Países BajosFil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tirado González, Irene. Medicine University of Berlin; AlemaniaFil: Conrad, Melanie L.. Medicine University of Berlin; AlemaniaFil: Rose, Matthias. Medicine University of Berlin; AlemaniaFil: Scherjon, S. A.. University of Groningen; Países BajosFil: Plösch, T.. University of Groningen; Países BajosFil: Blois, Sandra M.. Medicine University of Berlin; Alemani

A busca da qualidade na educação superior a distância no Brasil situação atual e algumas reflexões

Overview of the Education sector in Brazil, with focus on Higher Education. Number of enrolled students and the teachers’formation in Higher education. Causes of the growth of Distance Education(EAD) in the country and institutions of Higher Education accredited for offers of EAD. Definition for the EAD. The Regulation and the Indicators of Quality for EAD. The Brazilian legislation of EAD. The evaluation of programs and courses of EAD. Diplomas of  courses accomplished in foreign institutions. The quality criteria recommended by the Ministry of Education for EAD. Points to reflection on the approached themes.Panorama da Educação no Brasil, com destaque para a Educação Superior. Número de alunos matriculados e formação dos docentes no ensino superior. Causas do crescimento da Educação a Distância no país e instituições de Educação Superior credenciadas para ofertas de EAD. Definição para a EAD. A Regulamentação e os Referenciais de Qualidade para a EAD. A legislação em vigor no país. A avaliação de programas e cursos de EAD. Diplomas de cursos realizados em instituições estrangeiras. Os critérios de qualidade recomendados pelo Ministério da Educação para a EAD. Pontos para reflexão sobre os temas abordados

Regulation of the immunotolerance during the early stages of pregnancy

Einer der beeindruckensten Vorgänge hinsichtlich immunologischer Regulationsmechanismen ist die maternale Immuntoleranz gegenüber dem fetalen Semi-Allograft während der Schwangerschaft, auch tituliert als die „Schwangerschafts-Pause des Immunsystems“. Das Tolerieren des Fötus durch das mütterliche Immunsystem ergibt sich aus einem komplexen Zusammenspiel von Steroidhormonen, Zytokinen und weiteren Faktoren, die die Funktion der Immunzellen an der fetalen-maternalen Grenzzone regulieren. Beispielsweise werden niedrige Progesteron- und Th2- Zytokinspiegel und hohe Th1-Zytokinspiegel mit einer erhöhten Fehlgeburtenrate in Verbindung gebracht. Dieses Hormon- und Zytokinprofil kann durch psychosozialen Stress getriggert werden. Interessanterweise können die abortogenen Effekte, induziert durch Stress, mit Hilfe von Dydrogesteron aufgehoben werden. Es handelt sich hierbei um ein Progesteron-Derivat mit hoher Selektivität für den Progesteron- Rezeptor, das die Abnahme abortogen wirkender Zytokine wie TNF-α, IL-12 und IFN-γ bewirkt. Die Abstossung des Fötus wird unter anderem vom Zusammenspiel zwischen ICAM-1, das von Antigen-präsentierenden Zellen exprimiert wird, und seinem Liganden LFA-1 vermittelt: Die ICAM-1/ LFA-1-Interaktion führt zu einer interzellulärer Adhäsion, welche eine Rekrutierung von pro-inflammatorischer Zellen zur Implantationsstelle bewirkt sowie die Reifung von DZ in der Dezidua fördert. Schließlich wird durch die Reifung von DZ eine weitere Polarisierung des lokalen Zytokinprofils hin zum inflammatorischen Th1-Profil hervorgerufen. Die Blockade dieses Mechanismus resultiert in der Wiederherstellung von Immunakzeptanz in gestörten Schwangerschaften. Gezeigt werden konnte, dass Progesteron in Synergie mit Gal-1, einem immunmodulatorischen, Glykan- bindenden Protein, agiert: Bei reduzierter Gal- 1-Expression während der gestörten Schwangerschaft kann die Behandlung mit rekombinantem Gal-1 den Schwangerschaftsverlust verhindern. Die Immunakzeptanz wird über multiple Mechanismen wiederhergestellt, u. a. durch die Induktion toleranzbildender DZ, die wiederum in vivo die Expansion von IL- 10 produzierender regulatorischer T-Zellen vermitteln. An Schleimhautoberflächen wird die Immunantwort durch Antigenpräsentierende Zellen determiniert, hier findet der Erstkontakt mit dem fremden Antigen statt. In der Dezidua stellen die DC während der Schwangerschaft die entscheidende regulierende Population dar. Sie haben die Fähigkeit, mit anderen Komponenten des uterinen Signalnetzwerkes, z. B. den natürlichen Killerzellen, zu interagieren und die Immunantwort im Sinne einer stimulatorischen oder toleranzbildenden Art und Weise zu modulieren. Studien haben gezeigt, dass die DZ-NK-Interaktion in ein toleranzbildendes Spektrum resultieren kann. Dieses Spektrum ist charakterisiert durch herabregulierte Aktivierungsmarker auf uterinen NK-Zellen und DZ mit gleichzeitiger Dominanz Schwangerschafts-protektiver Th2-Zytokine. Die Interaktion von NK und DZ beeinflusst auch die uterine Zellproliferation. Dieser Prozess wird stark moduliert durch Signale die vom Trophoblasten ausgesendet werden. Die wichtige Rolle von DZ während der frühen Schwangerschaft wurde zudem in in vivo Studien untersucht, die zeigten, dass die transiente Depletion von CD11c positiven Zellen (z. B. durch die Gabe von Diphtherie-Toxin) den Implantationsprozess in Mäusen stört und in einer reduzierten Zucht-Fähigkeit resultiert. Die Reifung von uterinen NK-Zellen wird an DZ-depletierten Implantationsstellen unterbunden. Das spiegelte sich in einer reduzierten Perforin-Expression sowie einer verminderten Anzahl von PAS positiven Zellen wieder. Die Depletion von DZ in der Implantationsphase verursachte Anomalien in der Entwicklung der Plazenta (Hypozellularität von Spongiotrophoblast-Zellen und Labyrinth-Zellen, reduzierte Anzahl von Trophoblast-Riesenzellen). Zudem werden zwei charakteristische Marker der Trophoblast-Differenzierung (plazentare Laktogen-1 sowie Proliferin) herabreguliert. Zusammenfassend spielen die Funktionen der DZ und ihre Interaktionen mit dem dezidualen Mikromilieu eine wichtige Rolle um das Gelingen einer Schwangerschaft zu unterstützen.Successful mammalian pregnacy relies on the development of maternal immune tolerance towards the fetal semiallograft, which has been referred to as immunity's pregnant pause. Fetal tolerance results from a complex interplay involving steroid hormones, cytokines and other soluble factors that modulate leukocyte functions at the maternal fetal interface. For instance, low levels of progesterone and predominance of Th1 type cytokines have often been associated with increased abortion rates, which can also be boosted by psychoemotional stress. In mice, the abortogenic effects of stress can be counteracted by treatment with dydrogesterone (a progesterone derivative highly selective for the progesterone receptor), decreasing the frequency of abortogenic cytokines such as TNF-α, IL-12 and IFN-γ. Experiments in vivo have also shown that stress-triggered fetal rejection can be prevented by interfering with the molecular cross talk between ICAM-1, expressed on antigen presenting cells and its ligand, LFA-1, restoring immune acceptance mechanisms in challenged pregnancies. Intercellular adhesion events involving the ICAM-1/LFA-1 pathway mediate the recruitment of proinflammatory cells to the implantation site, promote dendritic cell (DC) maturation in the decidua, and subsequently induce additional local Th1 polarization via mature DCs. More recently, progesterone has been shown to act in synergy with Galectin (Gal)-1 (an immunoregulatory glycan-binding protein) to promote fetal tolerance. Consistently with a marked decrease in Gal-1 expression during failing pregnancies, treatment with recombinant Gal-1 restored fetal immune acceptance through multiple mechanisms, including the induction of tolerogenic DC, which in turn promoted the expansion of interleukin-10 (IL-10)-secreting regulatory T cells in vivo. Antigen presenting cells, mediating the first encounter with non-self antigens, are likely to be the core of immunoregulatory mechanisms acting on mucosal surfaces. Particularly in the decidua, DC have emerged as an important regulatory population given their ability to interact with other cellular components of the uterine milieu (i.e., natural killer cells) and modulate the nature of immune responses in stimulatory or tolerogenic fashion. Studies in vitro have shown that such DC-NK cell cross talk can result in the promotion of a tolerogenic microenvironment characterized by downregulation of the expression of activation markers on uterine NK cells and DC and dominance of pregnancy-protective Th2 cytokines. NK and DC interactions were also shown to influence uterine cell proliferation, providing the first clues into a role played by these cells during the process of endometrial decidualization. The important role played by DC during early pregnancy was further highlighted by studies in vivo showing that transient depletion of CD11c+ cells (i.e., through administration of diphtheria toxin) impairs the implantation process in mice, resulting in a reduced breeding efficiency. The analysis of DC- depleted implantation sites further revealed impairments in the maturation of uterine NK cell precursors, as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. Depletion of DC during the implantation process resulted in substantial anomalies in decidual and placental development, including defective vascular development as well as hypocellularity of the spongiotrophoblast and labyrinthine layers and impaired differentiation of trophoblast giant cells. In view of these findings, DC functions and their interactions within the decidualizing microenvironment are of critical importance to support a successful pregnancy outcome

Electron and Spin Transport in the Presence of Complex Absorbing Potential

We examine the impact of a complex absorbing potential on electron transport, both in the continuum and on a lattice. This requires the use of non-Hermitian Hamiltonians; the required formalism is briefly outlined. The lattice formulation allows us to study the interesting problem of an electron interacting with a stationary spin, and the subsequent time evolution of the electron and spin properties as the electron is absorbed after the initial interaction. Remarkably, the properties of the localized spin are affected 'at-a-distance' by the interaction of the (now entangled) electron with a complex potential.Comment: to be published in Phys. Rev.

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression

Role of galectin-glycan circuits in reproduction: from healthy pregnancy to preterm birth (PTB)

Growing evidence suggests that galectins, an evolutionarily conserved family of glycan-binding proteins, fulfill key roles in pregnancy including blastocyst implantation, maternal-fetal immune tolerance, placental development, and maternal vascular expansion, thereby establishing a healthy environment for the growing fetus. In this review, we comprehensively present the function of galectins in shaping cellular circuits that characterize a healthy pregnancy. We describe the current understanding of galectins in term and preterm labor and discuss how the galectin-glycan circuits contribute to key immunological pathways sustaining maternal tolerance and preventing microbial infections. A deeper understanding of the glycoimmune pathways regulating early events in preterm birth could offer the broader translational potential for the treatment of this devastating syndrome

Early thinning experiments established by the Fort Valley Experimental Forest

Between 1925 and 1936, the Fort Valley Experimental Forest (FVEF) scientists initiated a study to examine a series of forest thinning experiments in second growth ponderosa pine stands in Arizona and New Mexico. These early thinning plots furnished much of the early background for the development of methods used in forest management in the Southwest. The plots ranged from 0.1 ac to 5 ac (0.04 ha to 2.02 ha) in size and many of the thinning plots and control plots were remeasured at 2 to 10-year intervals until the 1940s. The first thinning plots in the Southwest, called the White Spar plots, were established in 1925 on the Prescott National Forest. The residual trees on the thinned White Spar plots maintained higher growth rates than the control until the mid 1970s. The results from these early stand thinning experiments led G.A. Pearson, Director of FVEF, and others to largely abandon uniform thinning treatments and adopt the crop-tree thinning method as an improved method for thinning southwestern ponderosa pine stands