3,768 research outputs found
The T allele of the hepatic lipase promoter variant C-480T is associated with increased fasting lipids and HDL and increased preprandial and postprandial LpCIII:B : European Atherosclerosis Research Study (EARS) II
The common C-480T transition in the hepatic lipase (HL) promoter has been
shown to be associated with lower HL activity and increased high density
lipoprotein (HDL) cholesterol. We examined the frequency and lipid
associations of this HL polymorphism in 385 healthy, young (18- to
28-year-old) men whose fathers had had a premature myocardial infarction
(designated cases) and 405 age-matched controls. These individuals were
participants in the European Atherosclerosis Research Study II
postprandial trial, who had been recruited from 11 European countries in 4
regions (the Baltic; United Kingdom; and central and southern Europe).
Overall, the frequency of the T allele was 0.207 in controls and 0.244 in
cases (P=0.08). The T allele was associated with higher fasting plasma
total cholesterol (P<0.01), triglycerides (P<0.01), and HDL cholesterol
(P<0.01). The strongest association was found with apolipoprotein (apo)
A-I concentration, which was 10% higher in individuals homozygous for the
T allele compared with those homozygous for the C allele (P<0.001). This
polymorphism had no effect on the rise in plasma triglyceride levels after
a fatty meal. However, before and after the fat load was ingested, levels
of particles containing both apoC-III and apoB (LpC-III:B) were higher in
carriers of the T allele, with homozygotes having 23% and 27% higher
levels preprandially and postprandially, respectively, than those
homozygous for the C allele (P<0.05). Thus, our results demonstrate that
the C-480T polymorphism in the HL promoter is associated with alterations
in plasma lipids and lipoproteins and the accumulation of atherogenic
LpC-III:B particles
The impact of heavy-quark loops on LHC dark matter searches
If only tree-level processes are included in the analysis, LHC monojet
searches give weak constraints on the dark matter-proton scattering cross
section arising from the exchange of a new heavy scalar or pseudoscalar
mediator with Yukawa-like couplings to quarks. In this letter we calculate the
constraints on these interactions from the CMS 5.0/fb and ATLAS 4.7/fb searches
for jets with missing energy including the effects of heavy-quark loops. We
find that the inclusion of such contributions leads to a dramatic increase in
the predicted cross section and therefore a significant improvement of the
bounds from LHC searches.Comment: 12 pages, 1 table, 3 figures, v2: extended discussion and improved
relic density calculation - matches published versio
Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model
Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific, cell-count scoring of histological sections from each eye as a measure of disease severity. Here, we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis. This allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate, protein analysis on ocular supernatants and qPCR on remnant tissues of the same eye. Dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model. To validate the technique, dose-responsive suppression of leukocyte infiltration by recombinant interleukin-10 was demonstrated, as well as selective suppression of the monocyte (CD11b+Ly6C+) infiltrate, in mice deficient for eitherCcl2orCcr2 Optical coherence tomography (OCT) was used for the first time in this model to allowin vivoimaging of infiltrating vitreous cells, and correlated with CD11b+Ly6G+ counts to provide another unique measure of cell populations in the ocular tissue. Multimodal tissue analysis of EIU is proposed as a new standard to improve and broaden the application of this model
Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).
<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p
Fast fluorescence microscopy for imaging the dynamics of embryonic development
Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field
Laser cooling of a diatomic molecule
It has been roughly three decades since laser cooling techniques produced
ultracold atoms, leading to rapid advances in a vast array of fields.
Unfortunately laser cooling has not yet been extended to molecules because of
their complex internal structure. However, this complexity makes molecules
potentially useful for many applications. For example, heteronuclear molecules
possess permanent electric dipole moments which lead to long-range, tunable,
anisotropic dipole-dipole interactions. The combination of the dipole-dipole
interaction and the precise control over molecular degrees of freedom possible
at ultracold temperatures make ultracold molecules attractive candidates for
use in quantum simulation of condensed matter systems and quantum computation.
Also ultracold molecules may provide unique opportunities for studying chemical
dynamics and for tests of fundamental symmetries. Here we experimentally
demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using
an optical cycling scheme requiring only three lasers, we have observed both
Sisyphus and Doppler cooling forces which have substantially reduced the
transverse temperature of a SrF molecular beam. Currently the only technique
for producing ultracold molecules is by binding together ultracold alkali atoms
through Feshbach resonance or photoassociation. By contrast, different proposed
applications for ultracold molecules require a variety of molecular
energy-level structures. Our method provides a new route to ultracold
temperatures for molecules. In particular it bridges the gap between ultracold
temperatures and the ~1 K temperatures attainable with directly cooled
molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams).
Ultimately our technique should enable the production of large samples of
molecules at ultracold temperatures for species that are chemically distinct
from bialkalis.Comment: 10 pages, 7 figure
Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes
Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.
Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.
Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).
Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points
Clustering in surgical trials : database of intracluster correlations
PMID: 22217216 [PubMed - indexed for MEDLINE] PMCID: PMC3311136 Free PMC ArticlePeer reviewedPublisher PD
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