Discovery of Mount Mazama cryptotephra in Lake Superior (North America): Implications and potential applications

Tephrochronology is a widely applied method recognized for its exceptional precision in geologic dating and stratigraphic correlation. Tephra from the ~7.6 kyr B.P. Mount Mazama caldera-forming (”climactic”) eruption have been widely identified and applied as stratigraphic isochrons sediments of northwestern North America, as well as in the Greenland ice core records. Recent findings of a microscopic tephra accumulation, or cryptotephra, from Mazama in Newfoundland indicated that this horizon should also be found in Lake Superior sediments. We present findings that confirm the presence of Mazama ash in two sediment cores from the Lake Superior basin, which indicates its likely presence in the rest of the Laurentian Great Lakes and in deposits throughout much of eastern North America and beyond. The ubiquity of this stratigraphic horizon should be applicable to a higher resolution evaluation of climatological, ecological, and archaeological events during the early- to mid-Holocene thermal maximum throughout much of North America.This research was supported by a Regents Professor grant by the University of Minnesota to Johnso

The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared

Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model -- an optically thick disk which is heated locally by the dissipation of gravitational binding energy -- is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty was that, toward the infrared, the disk spectrum starts to be hidden under strong hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emiting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. The model problems at shorter wavelengths should then be directed toward a better understanding of the inner parts of the revealed disk. The newly uncovered disk emission at large radii, with more future measurements, will also shed totally new light on the unanswered critical question of how and where the disk ends.Comment: published in Nature, 24 July 2008 issue. Supplementary Information can be found at http://www.mpifr-bonn.mpg.de/div/ir-interferometry/suppl_info.pdf Published version can be accessed from http://www.nature.com/nature/journal/v454/n7203/pdf/nature07114.pd

The Patient Enablement Instrument-French version in a family practice setting: a reliability study

Background: Patient enablement can be defined as the extent to which a patient is capable of understanding and coping with his or her health issues. This concept is linked to a number of health outcomes such as self-management of chronic diseases and quality of life. The Patient Enablement Instrument (PEI) was designed to measure this concept after a medical consultation. The instrument, in its original form and its translations into several languages, has proven to be reliable and valid. The purpose of this study was to evaluate the reliability of the French version of the PEI (PEI-Fv) in a family practice setting. Methods: One hundred and ten participants were recruited in a family medicine clinic in the Saguenay region of Quebec (Canada). The PEI-Fv was completed twice, immediately after consultation with a physician (T1) and 2 weeks after the consultation (T2). The internal consistency of the tool was assessed with Cronbach's α and test-retest reliability by intraclass correlation coefficient. Results: The mean score for the PEI-Fv was 5.06 ± 3.97 (95% confidence interval [CI]: 4.30-5.81) at T1 and 4.63 ± 3.90 (95% CI: 3.82-5.44) at T2. Cronbach's α was high at T1 (α1 = 0.93; 95% CI: 0.91-0.95) and T2 (α2 = 0.93; 95% CI: 0.91-0.95). The intraclass correlation coefficient was 0.62 (95% CI: 0.48-0.74), indicating a moderate test-retest reliability. Conclusions: The internal consistency of the PEI-Fv is excellent. Test-retest reliability was moderate to good. Test-retest reliability should be examined in further studies at a less than 2-week interval to reduce maturation bias. This instrument can be used to measure enablement after consultation in a French-speaking family practice setting

Validation of the World Health Organization Tool for Situational Analysis to Assess Emergency and Essential Surgical Care at District Hospitals in Ghana

The World Health Organization (WHO) Tool for Situational Analysis to Assess Emergency and Essential Surgical Care (hereafter called the WHO Tool) has been used in more than 25 countries and is the largest effort to assess surgical care in the world. However, it has not yet been independently validated. Test–retest reliability is one way to validate the degree to which tests instruments are free from random error. The aim of the present field study was to determine the test–retest reliability of the WHO Tool. The WHO Tool was mailed to 10 district hospitals in Ghana. Written instructions were provided along with a letter from the Ghana Health Services requesting the hospital administrator to complete the survey tool. After ensuring delivery and completion of the forms, the study team readministered the WHO Tool at the time of an on-site visit less than 1 month later. The results of the two tests were compared to calculate kappa statistics for each of the 152 questions in the WHO Tool. The kappa statistic is a statistical measure of the degree of agreement above what would be expected based on chance alone. Ten hospitals were surveyed twice over a short interval (i.e., less than 1 month). Weighted and unweighted kappa statistics were calculated for 152 questions. The median unweighted kappa for the entire survey was 0.43 (interquartile range 0–0.84). The infrastructure section (24 questions) had a median kappa of 0.81; the human resources section (13 questions) had a median kappa of 0.77; the surgical procedures section (67 questions) had a median kappa of 0.00; and the emergency surgical equipment section (48 questions) had a median kappa of 0.81. Hospital capacity survey questions related to infrastructure characteristics had high reliability. However, questions related to process of care had poor reliability and may benefit from supplemental data gathered by direct observation. Limitations to the study include the small sample size: 10 district hospitals in a single country. Consistent and high correlations calculated from the field testing within the present analysis suggest that the WHO Tool for Situational Analysis is a reliable tool where it measures structure and setting, but it should be revised for measuring process of care

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50=12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity