175 research outputs found
Comparative analysis of family consent to tissue donation according to two different donation form structures
Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line
This article is made available through the Brunel Open Access Publishing Fund. Copyright: © 2013 Mahajan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of
inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis,
oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and
clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic
cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia
cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D
and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and timedependent
apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz.
activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2)
showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D
induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SPD
in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of
survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a
drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in
AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis.
The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from
healthy controls was not affected. The study suggests involvement of SP-D in hostâs immunosurveillance and
therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.Department of Biotechnology, Indi
Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus
Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individualsâ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-Îł and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Investigaciones BiolĂłgicas y TecnolĂłgicas. Universidad Nacional de CĂłrdoba. Facultad de Ciencias Exactas, FĂsicas y Naturales. Instituto de Investigaciones BiolĂłgicas y TecnolĂłgicas; ArgentinaFil: Estevez, Inma. Centro de InvestigaciĂłn. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Investigaciones BiolĂłgicas y TecnolĂłgicas. Universidad Nacional de CĂłrdoba. Facultad de Ciencias Exactas, FĂsicas y Naturales. Instituto de Investigaciones BiolĂłgicas y TecnolĂłgicas; Argentin
Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients
Background
Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive.
Methods
We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted.
Results
Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JBâs atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion.
Conclusions
Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed
Gynecologic oncology patients' satisfaction and symptom severity during palliative chemotherapy
BACKGROUND: Research on quality and satisfaction with care during palliative chemotherapy in oncology patients has been limited. The objective was to assess the association between patient's satisfaction with care and symptom severity and to evaluate test-retest of a satisfaction survey in this study population. METHODS: A prospective cohort of patients with recurrent gynecologic malignancies receiving chemotherapy were enrolled after a diagnosis of recurrent cancer. Patients completed the Quality of End-of-Life care and satisfaction with treatment scale (QUEST) once upon enrollment in an outpatient setting and again a week later. Patients also completed the Mini-Mental Status Exam, the Hospital Anxiety/Depression Scale, a symptom severity scale and a demographic survey. Student's t-test, correlation statistics and percent agreement were used for analysis. RESULTS: Data from 39 patients were analyzed. Mean (SD) quality of care summary score was 41.95 (2.75) for physicians and 42.23 (5.42) for nurses (maximum score was 45; p = 0.76 for difference in score between providers). Mean (SD) satisfaction of care summary score was 29.03 (1.92) for physicians and 29.28 (1.70) for nurses (maximum score was 30; p = 0.49 for difference between providers). Test-retest for 33 patients who completed both QUEST surveys had high percent agreement (74â100%), with the exception of the question regarding the provider arriving late (45 and 53%). There was no correlation between quality and satisfaction of care and symptom severity. Weakness was the most common symptom reported. Symptom severity correlated with depression (r = 0.577 p < 0.01). There was a trend towards a larger proportion of patients reporting pain who had three or more prior chemotherapy regimens (p = 0.075). Prior number of chemotherapy regimens or time since diagnosis was not correlated with symptom severity score. Anxiety and depression were correlated with each other (r = 0.711, p < 0.01). There was no difference in symptom severity score at enrollment between those patients who have since died (n = 19) versus those who are still alive. CONCLUSION: The QUEST Survey has test-retest reliability when used as a written instrument in an outpatient setting. However, there was no correlation between this measure and symptom severity. Patient evaluation of care may be more closely related to the interpersonal aspects of the health care provider relationship than it is to physical symptoms
Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope
We report on the search for 0.1-10 GeV emission from magnetars in 17 months
of Fermi Large Area Telescope (LAT) observations. No significant evidence for
gamma-ray emission from any of the currently-known magnetars is found. The most
stringent upper limits to date on their persistent emission in the Fermi-LAT
energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on
the source. We also searched for gamma-ray pulsations and possible outbursts,
also with no significant detection. The upper limits derived support the
presence of a cut-off at an energy below a few MeV in the persistent emission
of magnetars. They also show the likely need for a revision of current models
of outer gap emission from strongly magnetized pulsars, which, in some
realizations, predict detectable GeV emission from magnetars at flux levels
exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch
D., Rea N., Burnett
Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi
We report the detection of high-energy gamma-ray emission from two starburst
galaxies using data obtained with the Large Area Telescope on board the Fermi
Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been
detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from
sources positionally coincident with locations of the starburst galaxies M82
and NGC 253. The total fluxes of the sources are consistent with gamma-ray
emission originating from the interaction of cosmic rays with local
interstellar gas and radiation fields and constitute evidence for a link
between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter
Fermi Gamma-ray Imaging of a Radio Galaxy
The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating
from the giant radio lobes of the radio galaxy Centaurus A. The resolved
gamma-ray image shows the lobes clearly separated from the central active
source. In contrast to all other active galaxies detected so far in high-energy
gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the
total source emission. The gamma-ray emission from the lobes is interpreted as
inverse Compton scattered relic radiation from the cosmic microwave background
(CMB), with additional contribution at higher energies from the
infrared-to-optical extragalactic background light (EBL). These measurements
provide gamma-ray constraints on the magnetic field and particle energy content
in radio galaxy lobes, and a promising method to probe the cosmic relic photon
fields.Comment: 27 pages, includes Supplementary Online Material; corresponding
authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar
Fermi Large Area Telescope observations of PSR J1836+5925
The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly
unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments
of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic
plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8
million years, a spindown luminosity of 1.1 erg s, and a
large off-peak emission component, making it quite unusual among the known
gamma-ray pulsar population. We present an analysis of one year of LAT data,
including an updated timing solution, detailed spectral results and a long-term
light curve showing no indication of variability. No evidence for a surrounding
pulsar wind nebula is seen and the spectral characteristics of the off-peak
emission indicate it is likely magnetospheric. Analysis of recent XMM
observations of the X-ray counterpart yields a detailed characterization of its
spectrum, which, like Geminga, is consistent with that of a neutron star
showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
- âŠ