940 research outputs found
Ischemia monitoring in off-pump coronary artery bypass surgery using intravascular near-infrared spectroscopy
BACKGROUND: In off-pump coronary artery bypass surgery, manipulations on the beating heart can lead to transient interruptions of myocardial oxygen supply, which can generate an accumulation of oxygen-dependent metabolites in coronary venous blood. The objective of this study was to evaluate the reliability of intravascular near-infrared spectroscopy as a monitoring method to detect possible ischemic events in off-pump coronary artery bypass procedures. METHODS: In 15 elective patients undergoing off-pump myocardial revascularization, intravascular near-infrared spectroscopic analysis of coronary venous blood was performed. NIR signals were transferred through a fiberoptic catheter for signal emission and collection. For data analysis and processing, a miniature spectrophotometer with multivariate statistical package was used. Signal acquisition and analysis were performed before and after revascularization. Spectroscopic data were compared with hemodynamic parameters, electrocardiogram, transesophageal echocardiography and laboratory findings. RESULTS: A conversion to extracorporeal circulation was not necessary. The mean number of grafts per patient was 3.1 ± 0.6. An intraoperative myocardial ischemia was not evident, as indicated by electrocardiogram and transesophageal echocardiography. Continuous spectroscopic analysis showed reproducible absorption spectra of coronary sinus blood. Due to uneventful intraoperative courses, clear ischemia-related changes could be detected in none of the patients. CONCLUSION: Our initial results show that intravascular near-infrared spectroscopy can reliably be used for an online intraoperative ischemia monitoring in off-pump coronary artery bypass surgery. However, the method has to be further evaluated and standardized to determine the role of spectroscopy in off-pump coronary artery bypass surgery
A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road
Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes
Surprising dissimilarities in a newly formed pair of 'identical twin' stars
The mass and chemical composition of a star are the primary determinants of
its basic physical properties--radius, temperature, luminosity--and how those
properties evolve with time. Thus, two stars born at the same time, from the
same natal material, and with the same mass are 'identical twins,' and as such
might be expected to possess identical physical attributes. We have discovered
in the Orion Nebula a pair of stellar twins in a newborn binary star system.
Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to
within 2 percent. Here we report that these twin stars have surface
temperatures that differ by ~300K (~10%), and luminosities that differ by ~50%,
both at high confidence level. Preliminary results indicate that the stars'
radii also differ, by 5-10%. These surprising dissimilarities suggest that one
of the twins may have been delayed by several hundred thousand years in its
formation relative to its sibling. Such a delay could only have been detected
in a very young, definitively equal-mass binary system3 such as that reported
here. Our findings reveal cosmic limits on the age synchronisation of young
binary stars, often used as tests for the age calibrations of star-formation
models.Comment: Published in Nature, 19 June 200
Overexpressed TP73 induces apoptosis in medulloblastoma
Abstract
Background
Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth.
Methods
We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods.
Results
Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and sensitized them to cell death in response to chemotherapeutic agents.
Conclusion
These results indicate that primary medulloblastomas express significant levels of TP73 isoforms, and suggest that they can modulate the survival and genotoxic responsiveness of medulloblastomas cells
Solar-type dynamo behaviour in fully convective stars without a tachocline
In solar-type stars (with radiative cores and convective envelopes), the
magnetic field powers star spots, flares and other solar phenomena, as well as
chromospheric and coronal emission at ultraviolet to X-ray wavelengths. The
dynamo responsible for generating the field depends on the shearing of internal
magnetic fields by differential rotation. The shearing has long been thought to
take place in a boundary layer known as the tachocline between the radiative
core and the convective envelope. Fully convective stars do not have a
tachocline and their dynamo mechanism is expected to be very different,
although its exact form and physical dependencies are not known. Here we report
observations of four fully convective stars whose X-ray emission correlates
with their rotation periods in the same way as in Sun-like stars. As the X-ray
activity - rotation relationship is a well-established proxy for the behaviour
of the magnetic dynamo, these results imply that fully convective stars also
operate a solar-type dynamo. The lack of a tachocline in fully convective stars
therefore suggests that this is not a critical ingredient in the solar dynamo
and supports models in which the dynamo originates throughout the convection
zone.Comment: 6 pages, 1 figure. Accepted for publication in Nature (28 July 2016).
Author's version, including Method
A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy
Dwarf satellite galaxies are thought to be the remnants of the population of
primordial structures that coalesced to form giant galaxies like the Milky Way.
An early analysis noted that dwarf galaxies may not be isotropically
distributed around our Galaxy, as several are correlated with streams of HI
emission, and possibly form co-planar groups. These suspicions are supported by
recent analyses, and it has been claimed that the apparently planar
distribution of satellites is not predicted within standard cosmology, and
cannot simply represent a memory of past coherent accretion. However, other
studies dispute this conclusion. Here we report the existence (99.998%
significance) of a planar sub-group of satellites in the Andromeda galaxy,
comprising approximately 50% of the population. The structure is vast: at least
400 kpc in diameter, but also extremely thin, with a perpendicular scatter
<14.1 kpc (99% confidence). Radial velocity measurements reveal that the
satellites in this structure have the same sense of rotation about their host.
This finding shows conclusively that substantial numbers of dwarf satellite
galaxies share the same dynamical orbital properties and direction of angular
momentum, a new insight for our understanding of the origin of these most dark
matter dominated of galaxies. Intriguingly, the plane we identify is
approximately aligned with the pole of the Milky Way's disk and is co-planar
with the Milky Way to Andromeda position vector. The existence of such
extensive coherent kinematic structures within the halos of massive galaxies is
a fact that must be explained within the framework of galaxy formation and
cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1
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Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope
We present a new measurement of the kinematic Sunyaev-Zeldovich effect using
data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation
Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area,
we evaluate the mean pairwise baryon momentum associated with the positions of
50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A
non-zero signal arises from the large-scale motions of halos containing the
sample galaxies. The data fits an analytical signal model well, with the
optical depth to microwave photon scattering as a free parameter determining
the overall signal amplitude. We estimate the covariance matrix of the mean
pairwise momentum as a function of galaxy separation, using microwave sky
simulations, jackknife evaluation, and bootstrap estimates. The most
conservative simulation-based errors give signal-to-noise estimates between 3.6
and 4.1 for varying galaxy luminosity cuts. We discuss how the other error
determinations can lead to higher signal-to-noise values, and consider the
impact of several possible systematic errors. Estimates of the optical depth
from the average thermal Sunyaev-Zeldovich signal at the sample galaxy
positions are broadly consistent with those obtained from the mean pairwise
momentum signal.Comment: 15 pages, 8 figures, 2 table
TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
<p>Abstract</p> <p>Background</p> <p>Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer.</p> <p>The purpose of this study was to evaluate the impact of TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different K-Ras and B-Raf mutational status.</p> <p>Methods</p> <p>TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2. mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting and cell viability was analyzed by the MTT method.</p> <p>Results</p> <p>We found that mRNA and TAp73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when B-Raf is mutated. This was statistically significant and was also associated with higher cell viability after the treatment.</p> <p>Conclusions</p> <p>Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function.</p> <p>Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab.</p
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