Amino-terminal sequence of phenobarbital-inducible cytochrome P-450 from rabbit liver microsomes: Similarity to hydrophobic amino-terminal segments of preproteins

SummaryThe amino-terminal sequence of two electrophoretically homogeneous forms of rabbit liver microsomal cytochrome P-450, P-450LM2 and P-45LM4, has been examined by automated Edman degradation. Methionine is the amino terminus of P-450LM2, and 17 of the first 20 residues are hydrophobic, including two clusters of five consecutive leucines. The composition and sequence of this region are similar to those of the short-lived hydrophobic amino-terminal precursor segments of certain other proteins, especially myeloma immunoglobulin light chains and pancreatic zymogens. Multiple amino-terminal residues, including methionine, were detected for P-450LM4 suggesting the presence of several highly similar forms of P-450 or that partial proteolysis had occurred.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22857/1/0000419.pd

Contexto bioético de la venta de misoprostol en las farmacias y boticas del Perú

La presente es una investigación bibliográfica y tuvo como objetivos describir, comprender y analizar el contexto bioético de la venta del misoprostol en las farmacias y boticas del Perú. Se analizó la documentación científica así como oficial de instituciones públicas y privadas, nacionales e internacionales, como los riesgos para la salud y vida de la mujer del uso del misoprostol de manera clandestina, la vigencia de este medicamento en las terapias como protector de la mucosa gástrica, su venta en las farmacias y boticas de manera oficial y clandestina. Los resultados indicaron que sí existen por la venta del misoprostol al público transgresiones contra principios bioéticos y regulatorios que ponen en riesgo la vida y la salud de la mujer y del concebido. Las conclusiones proponen alternativas a los problemas bioéticos que plantea este medicamento en su venta en farmacias y boticas del Perú.Tesi

The North American tree-ring fire-scar network

Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America

Applying the Military Success Model to School Age Children

Given the enormity of stress and the impact of multiple deployments, the Military Success Model (MSM) was designed as a way of conceptualizing working with service members and their families. This article discusses the impact of deployment on children of military servicemembers. Further the impact of school counseling germane to working with students from military families is noted. A direct application of the MSM is discussed while working through the different phases illustrated through a case study. Lastly, implications for future use are discussed

Terminal sequences of lysosome solubilized pig liver cytochrome b5 reductase

SummaryLysosome solubilized pig liver cytochrome b5 reductase has the following twenty residues as NH2-terminal sequence: Ser-Thr-Pro-Ala-Ile-Thr-Leu-Glu-Asn-Pro-Asp-Ile-Lys-Tyr-Pro-Leu-Arg-Leu-Ile-Asp. The fragment is predicted to exist largely in the random conformation with 2 [beta]-bends at residues 9-12 and 14-17. The reductase fragment appears clean enough for complete sequence investigation and is very similar to cathepsin D-solubilized rabbit liver cytochrome b5 reductase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23164/1/0000089.pd

Locomotor activity and gait in aged mice deficient for type IX collagen

Osteoarthritis (OA) is a risk factor for physical inactivity and impaired mobility, but it is not well understood how these locomotor behaviors are affected by the age of onset of OA and disease severity. Male mice homozygous for a Col9a1 gene inactivation (Col9a1−/−) develop early onset knee OA, increased tactile pain sensitivity, and gait alterations by 9 mo of age. We hypothesized that aged Col9a1−/− mice would reduce joint pain by adopting locomotor behaviors that reduce both the magnitude and daily frequency of joint loading. We tested this hypothesis by evaluating gait and spontaneous locomotor activity in 15- to 17-mo-old male Col9a1−/− (n = 5) and Col9a1+/+(WT) (n = 5) mice using well-controlled measures of voluntary activity in overground and running wheel conditions, as well as studies of gait in a velocity-controlled treadmill. We found no difference due to genotype in freely chosen locomotor velocity, stride frequency, hindfoot duty factor, dark phase activity time, or dark-phase travel distance during overground, running wheel, or speed-matched treadmill locomotion. Interpretation of these findings is potentially confounded by the observation that WT mice have greater knee OA than Col9a1−/− mice in the lateral tibial plateau by 17 mo of age. When accounting for individual differences in knee OA, functional locomotor impairments in aged Col9a1−/− and WT mice are manifested as reductions in total locomotor activity levels (e.g., both distance traveled and time active), particularly for wheel running. These results support the concept that current disease status, rather than age of disease onset, is the primary determinant of impaired locomotor activity with aging

Murine gene expression profiles do not predict human radiation status.

<p>A) A Minority of Murine Radiation Response Genes Are Expressed in Humans. The scatterplot shows –log (P-value) for a Pearson test of correlation between radiation exposure dose and gene expression for each gene with a mouse-human analog. If mouse (y-axis) and human (x-axis) were identifying the same genes, then we would expect that the points would fall on a diagonal line. Approximately 9,000 mouse genes have clear human analogues on the U133A microarray. 3,353 genes have significant association with dose (p-value <.05 after correction for multiple testing). Of those, 109 genes are significantly associated in humans. B) Performance of the Murine Radiation Classifier Against Human PB Samples. We used penalized regression with individual genes as potential independent variables to build a model predicting radiation exposure dose in mice. However, using variable selection to build models that predict radiation in mice does not lead to models that predict radiation exposure in humans. <i>Panel i</i> shows the mean predicted radiation levels (+/− SEM) of human <i>ex vivo</i> irradiated blood samples at 6 hrs and 24 hrs. <i>Panel ii</i> shows the mean predicted radiation levels of human TBI patient samples. The x-axis shows the times after irradiation at which gene expression measurements were taken. Actual radiation doses are displayed by different colors. Note the overlap between predicted mean radiation values in each analysis.</p

A 15-gene classifier can predict radiation dose levels in mice.

<p>A) C57Bl6 mice were irradiated with the TBI dose levels indicated (colors shown) and PB was collected at the times post-irradiation shown on the X axis. The Y axis shows the radiation dose levels predicted by application of the classifier against the irradiated samples. Each dot represents the mean dose level with corresponding 99% confidence intervals about the mean. As shown, at each dose level tested and at every time point through 7 days (168 hrs), the classifier discriminated radiation dose with high accuracy. B) Neither GCSF nor LPS treatments confound the predictive capability of the classifier to predict murine radiation dose levels. The predicted radiation dose levels (y axis) are plotted against time (x axis) of murine PB samples treated with and without GCSF and LPS. C) The RMA normalized gene expression levels of i) IGH-6, ii) LOXL1 and iii) CDKN1A are shown over time following several different radiation dose levels in mice and <i>ex vivo</i> with and without LPS treatment. While IGH-6 expression decreased in response to irradiation, LOXL1 expression increased promptly and CDKN1A was a late responsive gene.</p

CLPA Assay Reagents.

<p>CLPA Assay Reagents.</p