DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life

The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.

p53 Accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101

Functional inactivation of the tumor susceptibility gene tsg101 in NIH 3T3 fibroblasts results in cellular transformation and the ability to form metastatic tumors in nude mice. The N-terminal region of tsg101 protein is structurally similar to the catalytic domain of ubiquitin-conjugating enzymes, suggesting a potential role of tsg101 in ubiquitin-mediated protein degradation. The C-terminal domain of TSG101 can function as a repressor of transcription. To investigate the physiological function of tsg101, we generated a null mutation of the mouse gene by gene targeting. Homozygous tsg101−/− embryos fail to develop past day 6.5 of embryogenesis (E6.5), are reduced in size, and do not form mesoderm. Mutant embryos show a decrease in cellular proliferation in vivo and in vitro but no increase in apoptosis. Although levels of p53 transcripts were not affected in tsg101−/− embryos, p53 protein accumulated dramatically, implying altered posttranscriptional control of p53. In addition, transcription of the p53 effector, cyclin-dependent kinase inhibitor p21WAF-1/CIP-1, was increased 5- to 10-fold, whereas activation of MDM2 transcription secondary to p53 elevation was not observed. Introduction of a p53 null mutation into tsg101−/− embryos rescued the gastrulation defect and prolonged survival until E8.5. These results demonstrate that tsg101 is essential for the proliferative burst before the onset of gastrulation and establish a functional connection between tsg101 and the p53 pathway in vivo.

Spindle Dynamics and the Role of γ-Tubulin in Early Caenorhabditis elegans EmbryosV⃞

γ-Tubulin is a ubiquitous and highly conserved component of centrosomes in eukaryotic cells. Genetic and biochemical studies have demonstrated that γ-tubulin functions as part of a complex to nucleate microtubule polymerization from centrosomes. We show that, as in other organisms, Caenorhabditis elegans γ-tubulin is concentrated in centrosomes. To study centrosome dynamics in embryos, we generated transgenic worms that express GFP::γ-tubulin or GFP::β-tubulin in the maternal germ line and early embryos. Multiphoton microscopy of embryos produced by these worms revealed the time course of daughter centrosome appearance and growth and the differential behavior of centrosomes destined for germ line and somatic blastomeres. To study the role of γ-tubulin in nucleation and organization of spindle microtubules, we used RNA interference (RNAi) to deplete C. elegans embryos of γ-tubulin. γ-Tubulin (RNAi) embryos failed in chromosome segregation, but surprisingly, they contained extensive microtubule arrays. Moderately affected embryos contained bipolar spindles with dense and long astral microtubule arrays but with poorly organized kinetochore and interpolar microtubules. Severely affected embryos contained collapsed spindles with numerous long astral microtubules. Our results suggest that γ-tubulin is not absolutely required for microtubule nucleation in C. elegans but is required for the normal organization and function of kinetochore and interpolar microtubules.

Surréalisme Sous-L’Eau : science and surrealism in the early films and writings of Jean Painlevé

A French biologist who moved in Surrealist circles, Jean Painlevé began making films about underwater creatures in 1927, and by 1982 had created over two hundred films on a broad range of natural, scientific, and political subjects. His underwater films remain the most ethereal and poetic works in his oeuvre, and he specifically used cinema to capture the mystery and wonder of nature.

Discovering a history : the school of art at the University of Denver

Discovering a History: The School of Art at the University of Denver explores the early history of art education in Denver, and the significance of visual art education at the University of Denver within that history beginning in 1865, when the first classes in art were offered, and ending in 1929 when the University acquired the Chappell School of Art—an independent art school—and appointed Vance Kirkland as director. This paper also explores competing art institutions, which at times posed great hindrances to the University. Further, it illustrates how the artists who taught at the University of Denver School of Art, such as Ida De Steiguer, Preston Powers, Emma Richardson Cherry, and Henry Read, were amongst the great contributors to Denver’s burgeoning artistic culture.

Graveyards to Glamour : Development of Sexualized Angel Imagery in American Art and Advertising

Images of female angels in American art and advertisements have been sexualized in the late twentieth and early twenty-­‐first centuries. Companies such as Victoria’s Secret have appropriated the image of female angels, which first appeared at the beginning of the nineteenth century, and clothed them in lingerie in order to sell a product. This Masters Research Paper explores the evolution of female angelic imagery in the United States in order to understand how and when the image of angels began to be sexualized and used in advertising. Angels in art have been studied extensively; however, there has been no work done which examines how the angels in art and advertising have been sexualized. Nor has any work been done to map the evolution of female angelic imagery in American art. This Masters Research Paper will fill that gap in scholarship.

"Fit Cradle of the Reviving Art": An inquiry into the the Evolving Material Reality of the Murals in the Camposanto of Pisa from the Perspective of their British Reception from the 17th to the 19th century

The Camposanto of Pisa is an extraordinarily complex and evocative monument, which has captured the imagination of pilgrims, both religious and secular, for centuries. The late Medieval and early Renaissance wall paintings that line the perimeter of the portico surrounding a vast inner courtyard, are unparalleled in early Italian art, not only for their striking variety of composition and narrative complexity, but also for the sheer grandeur of their proportion. However, the passage of time has scarred the structure of the Camposanto and inflicted terrible damage on its wall paintings. This thesis explores the material reality of the Camposanto as experienced over three centuries through the eyes of British travelers. In order to situate the Camposanto mural cycle within an historical and cultural context, the first chapter provides an overview of the construction and decoration of the monument. Notably, Giorgio Vasari (1511-1574), the Italian Humanist often recognized as the father of art history, included numerous descriptions of the Camposanto murals in his highly influential text Vite de' più eccellenti pittori, scultori, ed architettori. Accordingly, the second chapter provides an analysis of Vasari’s descriptions and reflects upon the influence that the Renaissance author may have had upon the subsequent British reception of the Camposanto murals. The third chapter utilizes three centuries of travel writing in order to investigate the aesthetic impact of the Camposanto mural cycle upon British tourists from the seventeenth through to the nineteenth century.

Gas demand for power generation peaked as early as 2010. CEPS Commentary, 12 February 2016

The outlook for natural gas demand is often considered bright, especially for gas used to generate electricity. This is because gas is the cleanest of all fossil fuels. The carbon intensity of modern gas-fired power stations is less than 50% that of modern coal plants. Moreover, gas-fired units are well-suited to follow rapid swings in supply and demand due to their flexibility. In the future, these balancing tasks will become more and more important given the intermittent character of the supply of wind and solar power. Gas seems to hold out the promise of being a key pillar of the energy transition and the perfect partner of renewables. Given the EU’s long-term climate policy goals, however, there is strong evidence that demand for gas for purposes of power generation peaked as early as 2010.

The truth lies within: the reconstructive value of inner livores in a homicide case.

Through the widespread use of postmortem computed tomography, inner livores of the lungs have become a frequently observed phenomenon in the field of forensic medicine. Yet their time-dependent development, notably in comparison with the widely studied external livores, remains poorly understood. We present a unique homicide case where the victim was discovered in supine position with correspondent external livores fixed exclusively on the rear side. Yet upon postmortem computed tomography, the victim presented pronounced inner livores within the depending dorsal areas of both lungs but also vertical sedimentation levels solely within the right lung, suggesting an initial right-hand side position and a postmortem re-positioning of the body. Interestingly, this was consistent with tangible hints of postmortem manipulation on-site. It is likely that this repositioning occurred sometime during the early postmortem interval (<6 h) as the external livores have completely rearranged to the final supine position. The presented case suggests different development patterns of inner and outer livores, highlighting the necessity for controlled studies that explore the formation and fixation processes of livor mortis in internal organs. A better understanding of these issues can prove useful in forensic examinations.