The Influence of Epidermal Growth Factor on Surface Morphology of Fetal Rat Hepatocytes in Primary Culture

In an attempt to understand the hormonal regulation of somatomedin secretion in the fetus, we have confirmed that epidermal growth factor (EGF) stimulates fetal rat hepatocytes in primary culture to secrete somatomedin in a time and a dose-dependent fashion. Transmission electron microscopy (TEM) revealed that the cultured cells had ultrastructural features consistent with those of fetal hepatocytes. Scanning electron microscopy (SEM) showed that cells grown in either Medium 199 or EGF supplemented Medium 199 formed cellular aggregates within 6 h. The surface features of cells in control and experimental cultures were indistinguishable up until 24 h after exposure to EGF. At this point in time, morphological differences between treatment groups were first apparent with SEM. In the presence of EGF, cellular aggregates were thicker, cells were more rounded in contour, and the number of microvilli and cytoplasmic excrescences (blebs) was greater than in control cultures. These differences were further accentuated at 48 h after exposure to the growth factor. Since the appearance of microvilli and blebs coincides with increasing production of somatomedin, they may represent morphological evidence of secretory activity

VLBI for Gravity Probe B. IV. A New Astrometric Analysis Technique and a Comparison with Results from Other Techniques

When very long baseline interferometry (VLBI) observations are used to determine the position or motion of a radio source relative to reference sources nearby on the sky, the astrometric information is usually obtained via1) phase-referenced maps or (2) parametric model fits to measured fringe phases or multiband delays. In this paper, we describe a “merged” analysis technique which combines some of the most important advantages of these other two approaches. In particular, our merged technique combines the superior model-correction capabilities of parametric model fits with the ability of phase-referenced maps to yield astrometric measurements of sources that are too weak to be used in parametric model fits. We compare the results from this merged technique with the results from phase-referenced maps and from parametric model fits in the analysis of astrometric VLBI observations of the radio-bright star IM Pegasi (HR 8703) and the radio source B2252+172 nearby on the sky. In these studies we use central-core components of radio sources 3C 454.3 and B2250+194 as our positional references. We obtain astrometric results for IM Peg with our merged technique even when the source is too weak to be used in parametric model fits, and we find that our merged technique yields astrometric results superior to the phase-referenced mapping technique. We used our merged technique to estimate the proper motion and other astrometric parameters of IM Peg in support of the NASA/Stanford Gravity Probe B mission.AstronomyPhysic

Effects of infection history on dengue virus infection and pathogenicity

The understanding of immunological interactions among the four dengue virus (DENV) serotypes and their epidemiological implications is often hampered by the lack of individuallevel infection history. Using a statistical framework that infers full infection history, we analyze a prospective pediatric cohort in Nicaragua to characterize how infection history modulates the risks of DENV infection and subsequent clinical disease. After controlling for age, one prior infection is associated with 54% lower, while two or more are associated with 91% higher, risk of a new infection, compared to DENV-naive children. Children >8 years old have 55% and 120% higher risks of infection and subsequent disease, respectively, than their younger peers. Among children with ≥1 prior infection, intermediate antibody titers increase, whereas high titers lower, the risk of subsequent infection, compared with undetectable titers. Such complex dependency needs to be considered in the design of dengue vaccines and vaccination strategies

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

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Teleost Growth Factor Independence (Gfi) Genes Differentially Regulate Successive Waves of Hematopoiesis

Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gfi1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors.Stem Cell and Regenerative Biolog