406 research outputs found
Gene expression profiling of breast tumours from New Zealand patients
AIMS: New Zealand has one of the highest rates of breast cancer incidence in the world. We investigated the gene expression profiles of breast tumours from New Zealand patients, compared them to gene expression profiles of international breast cancer cohorts and identified any associations between altered gene expression and the clinicopathological features of the tumours.
METHODS: Affymetrix microarrays were used to measure the gene expression profiles of 106 breast tumours from New Zealand patients. Gene expression data from six international breast cancer cohorts were collated, and all the gene expression data were analysed using standard bioinformatic and statistical tools.
RESULTS: Gene expression profiles associated with tumour ER and ERBB2 status, molecular subtype and selected gene expression signatures within the New Zealand cohort were consistent with those found in international cohorts. Significant differences in clinicopathological features such as tumour grade, tumour size and lymph node status were also observed between the New Zealand and international cohorts.
CONCLUSIONS: Gene expression profiles, which are a sensitive indicator of tumour biology, showed no clear diÂŹfference between breast tumours from New Zealand patients and those from non-New Zealand patients. This suggests that other factors may contribute to the high and increasing breast cancer incidence in New Zealand compared to international populations
SMN Protein Can Be Reliably Measured in Whole Blood with an Electrochemiluminescence (ECL) Immunoassay: Implications for Clinical Trials
Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5ÎŒL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, we measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets. We show that SMN protein levels in C/C-allele mice, which model a mild form of SMA, were high in neonatal stage, decreased in the first few weeks after birth, and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of the C/C-allele mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy
A Radio Search For Pulsar Companions To SDSS Low-Mass White Dwarfs
We have conducted a search for pulsar companions to 15 low-mass white dwarfs
(LMWDs; M < 0.4 M_Sun) at 820 MHz with the NRAO Green Bank Telescope (GBT).
These LMWDs were spectroscopically identified in the Sloan Digital Sky Survey
(SDSS), and do not show the photometric excess or spectroscopic signature
associated with a companion in their discovery data. However, LMWDs are
believed to evolve in binary systems and to have either a more massive WD or a
neutron star as a companion. Indeed, evolutionary models of low-mass X-ray
binaries, the precursors of millisecond pulsars (MSPs), produce significant
numbers of LMWDs (e.g., Benvenuto & De Vito 2005), suggesting that the SDSS
LMWDs may have neutron star companions. No convincing pulsar signal is detected
in our data. This is consistent with the findings of van Leeuwen et al. (2007),
who conducted a GBT search for radio pulsations at 340 MHz from unseen
companions to eight SDSS WDs (five are still considered LMWDs; the three others
are now classified as "ordinary" WDs). We discuss the constraints our
non-detections place on the probability P_MSP that the companion to a given
LMWD is a radio pulsar in the context of the luminosity and acceleration limits
of our search; we find that P_MSP < 10 +4 -2 %.Comment: 5 pages, 1 figure, 1 table; accepted for publication in the
Astrophysical Journa
Geological Field Trips
This field trip guide organized in the framework of the Goldschmidt Conference 2013, held in Florence from
August 25 to 30, 2013, is here presented.
The two-days field trip, shows some of the many geological, naturalistic and cultural features in the Fiorano
area (Modena), in which history, geology and passion for Ferrari come together in a perfect marriage.
The first excursion day is dedicated to visit the Natural Reserve of Salse di Nirano, where the mud volcanoes,
produced by the cold mud, salt water and hydrocarbons - mainly methane- can be observed.
The second day is devoted to visit the Ferrari Museum and goes on at the Spezzano Castle, hosting the Ceramics
Museum. Clays are, in fact, abundant in the hilly margin, where they form badlands, characteristic narrow crests
washed out by running waters. In the Castle there is also a Balsamic Vinegar producing Consortium, itâs a peculiar
and typical product of Modena province. The itinerary ends with the tour to Enzo Ferrariâs Birthplace at Modena
The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits
PMCID: PMC3410907This 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
Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6âmg/kg/day); (iii) Ramipril (DRam;3âmg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (nâ=â11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown
The Seventh Data Release of the Sloan Digital Sky Survey
This paper describes the Seventh Data Release of the Sloan Digital Sky Survey
(SDSS), marking the completion of the original goals of the SDSS and the end of
the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most
of the roughly 2000 deg^2 increment over the previous data release lying in
regions of low Galactic latitude. The catalog contains five-band photometry for
357 million distinct objects. The survey also includes repeat photometry over
250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A
coaddition of these data goes roughly two magnitudes fainter than the main
survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2
in the Northern Galactic Cap, closing the gap that was present in previous data
releases. There are over 1.6 million spectra in total, including 930,000
galaxies, 120,000 quasars, and 460,000 stars. The data release includes
improved stellar photometry at low Galactic latitude. The astrometry has all
been recalibrated with the second version of the USNO CCD Astrograph Catalog
(UCAC-2), reducing the rms statistical errors at the bright end to 45
milli-arcseconds per coordinate. A systematic error in bright galaxy photometr
is less severe than previously reported for the majority of galaxies. Finally,
we describe a series of improvements to the spectroscopic reductions, including
better flat-fielding and improved wavelength calibration at the blue end,
better processing of objects with extremely strong narrow emission lines, and
an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor
correction
The Fifth Data Release of the Sloan Digital Sky Survey
This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky
Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and
represents the completion of the SDSS-I project (whose successor, SDSS-II will
continue through mid-2008). It includes five-band photometric data for 217
million objects selected over 8000 square degrees, and 1,048,960 spectra of
galaxies, quasars, and stars selected from 5713 square degrees of that imaging
data. These numbers represent a roughly 20% increment over those of the Fourth
Data Release; all the data from previous data releases are included in the
present release. In addition to "standard" SDSS observations, DR5 includes
repeat scans of the southern equatorial stripe, imaging scans across M31 and
the core of the Perseus cluster of galaxies, and the first spectroscopic data
from SEGUE, a survey to explore the kinematics and chemical evolution of the
Galaxy. The catalog database incorporates several new features, including
photometric redshifts of galaxies, tables of matched objects in overlap regions
of the imaging survey, and tools that allow precise computations of survey
geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS
Sixth Data Release (DR6) is now public, available from http://www.sdss.or
The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III
The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with
new instrumentation and new surveys focused on Galactic structure and chemical
evolution, measurements of the baryon oscillation feature in the clustering of
galaxies and the quasar Ly alpha forest, and a radial velocity search for
planets around ~8000 stars. This paper describes the first data release of
SDSS-III (and the eighth counting from the beginning of the SDSS). The release
includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap,
bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a
third of the Celestial Sphere. All the imaging data have been reprocessed with
an improved sky-subtraction algorithm and a final, self-consistent photometric
recalibration and flat-field determination. This release also includes all data
from the second phase of the Sloan Extension for Galactic Understanding and
Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars
at both high and low Galactic latitudes. All the more than half a million
stellar spectra obtained with the SDSS spectrograph have been reprocessed
through an improved stellar parameters pipeline, which has better determination
of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from
submitted version
Synthetic Associations Are Unlikely to Account for Many Common Disease Genome-Wide Association Signals
Synthetic associations have been posited as a possible explanation for missing heritability in complex disease. We show several lines of evidence which suggest that, while possible, these synthetic associations are not common
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