1,730 research outputs found
ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants
This is the final version. Available on open access from Impact Journals via the DOI in this recordThe Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer's disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92Ă—10-14) and hypertension (OR=0.94, 95% CI: 0.92 to 0.97, p=7.28Ă—10-7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42Ă—10-92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.National Institute on Agin
ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population
Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12–1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population
Semi-analytical approach to magnetized temperature autocorrelations
The cosmic microwave background (CMB) temperature autocorrelations, induced
by a magnetized adiabatic mode of curvature inhomogeneities, are computed with
semi-analytical methods. As suggested by the latest CMB data, a nearly
scale-invariant spectrum for the adiabatic mode is consistently assumed. In
this situation, the effects of a fully inhomogeneous magnetic field are
scrutinized and constrained with particular attention to harmonics which are
relevant for the region of Doppler oscillations. Depending on the parameters of
the stochastic magnetic field a hump may replace the second peak of the angular
power spectrum. Detectable effects on the Doppler region are then expected only
if the magnetic power spectra have quasi-flat slopes and typical amplitude
(smoothed over a comoving scale of Mpc size and redshifted to the epoch of
gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic
energy spectra are bluer (i.e. steeper in frequency) the allowed value of the
smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The
implications of this investigation for the origin of large-scale magnetic
fields in the Universe are discussed. Connections with forthcoming experimental
observations of CMB temperature fluctuations are also suggested and partially
explored.Comment: 40 pages, 13 figure
Viroids: survivors from the RNA world?
[EN] Because RNA can be a carrier of genetic information and a biocatalyst, there
is a consensus that it emerged before DNA and proteins, which eventually
assumed these roles and relegated RNA to intermediate functions. If such a
scenarioÂżthe so-calledRNAworldÂżexisted,wemight hope to find its relics
in our presentworld. The properties of viroids that make them candidates for
being survivors of the RNA world include those expected for primitive RNA
replicons: (a) small size imposed by error-prone replication, (b) high G +
C content to increase replication fidelity, (c) circular structure for assuring
complete replication without genomic tags, (d ) structural periodicity for
modular assembly into enlarged genomes, (e) lack of protein-coding ability
consistent with a ribosome-free habitat, and ( f ) replication mediated in some
by ribozymes, the fingerprint of the RNA world. With the advent of DNA
and proteins, those protoviroids lost some abilities and became the plant
parasites we now know.R.F. has received funding by grant BFU2011-28443 from Ministerio de Economia y Competititvidad (MINECO, Spain), R.S. by grants BFU2011-25271 (MINECO) and ERC-2011-StG-281191-VIRMUT (European Research Council), and S.F.E. by grant BFU2012-30805 (MINECO). P.S. has been supported by postdoctoral contracts from Generalitat Valenciana (APOSTD/2010, program VALi+d) and MINECO (program Juan de la Cierva).Flores Pedauye, R.; Gago Zachert, SP.; Serra Alfonso, P.; Sanjuan Verdeguer, R.; Elena Fito, SF. (2014). Viroids: survivors from the RNA world?. Annual Review of Microbiology. 68:395-414. https://doi.org/10.1146/annurev-micro-091313-103416S3954146
Neo-Anal Sphincter Fabrication in the Rat
Undergraduate Research Opportunity Program (UROP)http://deepblue.lib.umich.edu/bitstream/2027.42/116119/1/Neo_Anal_SphincterFabrication_Rats.pd
Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors
In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors
Anisotropic Impurity-States, Quasiparticle Scattering and Nematic Transport in Underdoped Ca(Fe1-xCox)2As2
Iron-based high temperature superconductivity develops when the `parent'
antiferromagnetic/orthorhombic phase is suppressed, typically by introduction
of dopant atoms. But their impact on atomic-scale electronic structure, while
in theory quite complex, is unknown experimentally. What is known is that a
strong transport anisotropy with its resistivity maximum along the crystal
b-axis, develops with increasing concentration of dopant atoms; this
`nematicity' vanishes when the `parent' phase disappears near the maximum
superconducting Tc. The interplay between the electronic structure surrounding
each dopant atom, quasiparticle scattering therefrom, and the transport
nematicity has therefore become a pivotal focus of research into these
materials. Here, by directly visualizing the atomic-scale electronic structure,
we show that substituting Co for Fe atoms in underdoped Ca(Fe1-xCox)2As2
generates a dense population of identical anisotropic impurity states. Each is
~8 Fe-Fe unit cells in length, and all are distributed randomly but aligned
with the antiferromagnetic a-axis. By imaging their surrounding interference
patterns, we further demonstrate that these impurity states scatter
quasiparticles in a highly anisotropic manner, with the maximum scattering rate
concentrated along the b-axis. These data provide direct support for the recent
proposals that it is primarily anisotropic scattering by dopant-induced
impurity states that generates the transport nematicity; they also yield simple
explanations for the enhancement of the nematicity proportional to the dopant
density and for the occurrence of the highest resistivity along the b-axis
Comprehensive Study in the Inhibitory Effect of Berberine on Gene Transcription, Including TATA Box
Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box
- …