A Review of the Pikes Peak Batholith, Front Range, Central Colorado: A Type Example of A-Type Granitic Magmatism

The N 1.08-Ga Pikes Peak composite batholith of central Colorado is a type example of an Atype granitic system. From the 1970s through the 1990s, details of the field relations, mineralogy, major and trace element compositions, and isotopic geochemistry of Pikes Peak rocks were documented, and they reveal the existence of two chemical groups, a potassic and a sodic series. The potassic series (~64-78 wt % SiO2) includes the Pikes Peak Granite, which is mostly coarse-grained biotite f hornblende syenogranite and minor monzogranite that dominates the batholith. The potassic series also includes fine- to medium-grained biotite granite found in numerous, small, late-stage plutons throughout the batholith. The sodic series is found in seven plutons comprised of a wide range of rock types ( N 44-78 wt % SiO2), including gabbro, diabase, syenite/quartz syenite, and fayalite and sodic amphibole granite. Differences in petrologic and geochemical characteristics between the sodic and potassic series indicate different petrogenetic histories. Major and trace element and strontium and oxygen isotopic data were used by some workers to hypothesize that mantle-derived alkali basalt underwent crystal fractionation and reaction with lower crustal rocks to generate syenitic magmas of the sodic series, which subsequently underwent further fractionation to produce sodic granites. Recent studies involving estimates of oxygen fugacities, along with additional trace element and neodymium isotopic data, also support a basalt fractionation model for the sodic series, but suggest only minor crustal involvement. Gabbros and diabase dikes associated with the sodic series appear to have been derived from mantle sources that previously had been affected by a subduction event, based on neodymium isotopic and trace element data. Some workers propose that the potassic series also formed by fractionation of syenitic and/ or basaltic magmas coupled with reaction with intermediate rather than lower crust. Other workers propose a model in which genesis of the potassic series was dominated by partial melting involving tonalitic sources, with fractionation and-perhaps magma mixing playing subordinate roles in generating compositional diversity among the potassic granitoids. The Pikes Peak batholith thus formed by emplacement of at least two petrogenetically different granite types, which were emplaced close together in space and time and which exhibit geochemical characteristics typical of A-type granites

A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute approximately 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (\u3e99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin, and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung

Accretion Disks and the Lyman Continuum Polarization of QSOs

HST observations of some QSOs show a strong, abrupt increase in polarization at rest wavelength about 750 A, suggestive of a connection with the Lyman edge of hydrogen. Blaes and Agol (1996) have proposed an explanation in terms of stellar atmosphere effects in an accretion disk around a supermassive black hole. We have computed the polarized spectrum of a such a disk, including the effects of the relativistic transfer function. Relativistic effects add an additional blueshift of the polarization rise sufficient that the model cannot explain the observations. A good fit results if the emitted radiation is assumed to have a sharp increase in polarized flux at the Lyman edge in the rest frame of the orbiting gas. Relativistic effects then cause the observed polarization to rise sharply at a wavelength substantially less than 912 A. The blueshift depends on the angular momentum of the black hole and the inclination of the disk. A good fit to PG 1630+377 results from a simple model with a dimensionless angular momentum a = 0.5 and an observer viewing angle cos theta = 0.1. An intermediate value of a might result from coallescing black holes, successive accretion events, or electromagnetic extraction of angular momentum from the hole.Comment: 24 pages incl. 9 PostScript figures. Uses aaspp4.sty and flshrt.sty. To be published in The Astrophysical Journal, Vol. 496 (1988 April 1

Petrology and geochemistry of late-stage intrusions of the A-type, mid-Proterozoic Pikes Peak batholith (Central Colorado, USA): implications for petrogenetic models

The ~1.08 Ga anorogenic, A-type Pikes Peak batholith (Front Range, central Colorado) is dominated by coarse-grained, biotite ± amphibole syenogranites and minor monzogranites, collectively referred to as Pikes Peak granite (PPG). The batholith is also host to numerous small, late-stage plutons that have been subdivided into two groups (e.g. Wobus, 1976. Studies in Colorado Field Geology, Colorado School of Mines Professional Contributions, Colorado): (1) a sodic series (SiO2 = ~44–78 wt%; K/Na = 0.32–1.36) composed of gabbro, diabase, syenite/quartz syenite and fayalite and sodic amphibole granite; and (2) a potassic series (SiO2 = ~70–77 wt%; K/Na = 0.95–2.05), composed of biotite granite and minor quartz monzonite. Differences in major and trace element and Nd isotopic characteristics for the two series indicate different petrogenetic histories. Potassic granites of the late-stage intrusions appear to represent crustal anatectic melts derived from tonalite sources, based on comparison of their major element compositions with experimental melt products. In addition, Nd isotopic characteristics of the potassic granites [εNd (1.08 Ga) = −0.2 to −2.7] overlap with those for tonalites/granodiorites [ca 1.7 Ga Boulder Creek intrusions; εNd (1.08 Ga) = −2.4 to −3.6] exposed in the region. Some of the partial melts evolved by fractionation dominated by feldspar. The late-stage potassic granites share geochemical characteristics with most of the PPG, which is also interpreted to have an anatectic origin involving tonalitic crust. The origin of monzogranites associated with the PPG remains unclear, but mixing between granitic and mafic or intermediate magmas is a possibility. Syenites and granites of the sodic series cannot be explained as crustal melts, but are interpreted as fractionation products of mantle-derived mafic magmas with minor crustal input. High temperature and low oxygen fugacity estimates (e.g. Frost et al., 1988. American Mineralogist 73, 727–740) support a basalt fractionation origin, as do εNd values for sodic granitoids [εNd (1.08 Ga) = +2.2 to −0.7], which are higher than εNd values for Colorado crust at 1.08 Ga (ca −1.0 to −4.0). Enrichments in incompatible elements (e.g. rare earth elements, Rb, Y) and depletions in compatible elements (e.g. Cr, Sr, Ba) in the sodic granitoids compared to coeval mafic rocks are also consistent with fractionation. Accessory mineral fractionation, release of fluorine-rich volatiles and/or removal of pegmatitic fluids could have modified abundances of Ce, Nb, Zr and Y in some sodic granitoid magmas. Gabbros and mafic dikes associated with the sodic granitoids have εNd (1.08 Ga) of −3.0 to +3.5, which are lower than depleted mantle at 1.08 Ga, and their trace element characteristics suggest derivation from mantle sources that were previously affected by subduction-related processes. However, it is difficult to characterize the mantle component in these magmas, because assimilation of crust during magma ascent could also result in their observed geochemical features. The Pikes Peak batholith is composed of at least two petrogenetically different granite types, both of which exhibit geochemical characteristics typical of A-type granites. Models proposed for the petrogenesis of the granitoids imply the existence of mafic rocks at depth and addition of juvenile material to the crust in central Colorado at ~1.1 Ga

Substrate, sediment, and slope controls on bedrock channel geometry in postglacial streams

The geometry of channels controls the erosion rate of rivers and the evolution of topography following environmental change. We examine how sediment, slope, and substrate interact to constrain the development of channels following deglaciation and test whether theoretical relationships derived from streams reacting to tectonic uplift apply in these settings. Using an extensive data set of channel geometry measurements from postglacial streams in the Scottish Highlands, we find that a power law width-drainage area scaling model accounts for 81% of the spatial variation in channel width. Substrate influences channel form at the reach scale, with bedrock channels found to be narrower and deeper than alluvial channels. Bedrock channel width does not covary with slope, which may be due to downstream variations in sediment flux. Bedrock channel width-to-depth ratios increase with discharge (or area) and sediment flux, consistent with increasing bed cover promoting lateral widening. We find steep, wide, and shallow bedrock channels immediately below lakes, which we interpret as the result of limited erosion due to a lack of sediment tools. Where sediment supply is sufficient to exceed transport capacity, alluvial channels develop wider, shallower geometries constrained primarily by flow hydraulics. Our results indicate that simple scaling models of channel width with drainage area are applicable at regional scale, but locally, channel width varies with substrate, and in the case of bedrock channels, with sediment flux.

B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape.

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions

Inactivation of murine norovirus by chemical biocides on stainless steel

<p>Abstract</p> <p>Background</p> <p>Human norovirus (NoV) causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces.</p> <p>Methods</p> <p>The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells.</p> <p>Results</p> <p>PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)] were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by ≥ 4 log₁₀within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v). Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes).</p> <p>Conclusion</p> <p>Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces.</p

In Vivo Comparison of Two Human Norovirus Surrogates for Testing Ethanol-Based Handrubs: The Mouse Chasing the Cat!

Human noroviruses (HuNoV), a major cause of acute gastroenteritis worldwide, cannot be readily cultured in the lab. Therefore, a feline calicivirus (FCV) is often used as its surrogate to, among other things, test alcohol-based handrubs (ABHR). The more recent laboratory culture of a mouse norovirus (MNV) provides an alternative. While MNV is closer to HuNoV in several respects, to date, no comparative testing of FCV and MNV survival and inactivation on human hands has been performed. This study was designed to address the knowledge gap. The rates of loss in viability during drying on hands were −1.91 and −1.65% per minute for FCV and MNV, respectively. When the contaminated skin was exposed for 20 s to either a commercial ABHR with 62% (v/v) ethanol or to 75% (v/v) ethanol in water, FCV infectivity was reduced by <1 log10 while that of MNV by nearly 2.8 log10. Extending the contact time to 30 s reduced the FCV titer by almost 2 log10 by both test substances and that of MNV by >3.5 log10 by the commercial ABHR while 75% ethanol did not show any noticeable improvement in activity as compared to the 20 s contact. An 80% (v/v) aqueous solution of ethanol gave only a 1.75 log10 reduction in MNV activity after 20 s. The results show significant differences in the ethanol susceptibility of FCV and MNV in contact times relevant to field use of ABHR and also that 62% ethanol was a more effective virucide than either 75% or 80% ethanol. These findings indicate the need for a review of the continuing use of FCV as a surrogate for HuNoV

eXtraembryonic ENdoderm (XEN) Stem Cells Produce Factors that Activate Heart Formation

Initial specification of cardiomyocytes in the mouse results from interactions between the extraembryonic anterior visceral endoderm (AVE) and the nascent mesoderm. However the mechanism by which AVE activates cardiogenesis is not well understood, and the identity of specific cardiogenic factors in the endoderm remains elusive. Most mammalian studies of the cardiogenic potential of the endoderm have relied on the use of cell lines that are similar to the heart-inducing AVE. These include the embryonal-carcinoma-derived cell lines, END2 and PYS2. The recent development of protocols to isolate eXtraembryonic ENdoderm (XEN) stem cells, representing the extraembryonic endoderm lineage, from blastocyst stage mouse embryos offers new tools for the genetic dissection of cardiogenesis.Here, we demonstrate that XEN cell-conditioned media (CM) enhances cardiogenesis during Embryoid Body (EB) differentiation of mouse embryonic stem (ES) cells in a manner comparable to PYS2-CM and END2-CM. Addition of CM from each of these three cell lines enhanced the percentage of EBs that formed beating areas, but ultimately, only XEN-CM and PYS2-CM increased the total number of cardiomyocytes that formed. Furthermore, our observations revealed that both contact-independent and contact-dependent factors are required to mediate the full cardiogenic potential of the endoderm. Finally, we used gene array comparison to identify factors in these cell lines that could mediate their cardiogenic potential.These studies represent the first step in the use of XEN cells as a molecular genetic tool to study cardiomyocyte differentiation. Not only are XEN cells functionally similar to the heart-inducing AVE, but also can be used for the genetic dissection of the cardiogenic potential of AVE, since they can be isolated from both wild type and mutant blastocysts. These studies further demonstrate the importance of both contact-dependent and contact-independent factors in cardiogenesis and identify potential heart-inducing proteins in the endoderm