817 research outputs found
A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease
A Series of 4- and 5-Coordinate Ni(II) Complexes: Synthesis, Characterization, Spectroscopic, and DFT Studies
A series of four- and five-coordinate Ni(II) complexes CztBu(PyriPr)2NiX (1–3 and 1·THF–3·THF), where X = Cl, Br, and I, were synthesized and fully characterized by NMR and UV–vis spectroscopy, X-ray crystallography, cyclic voltammetry, and density functional theory calculations. The solid-state structures of 1–3 reveal rare examples of seesaw Ni(II) complexes. In solution, 1–3 bind reversibly to a THF molecule to form five-coordinate adducts. The electronic transitions in the visible region (630–680 nm), attributed to LMCT bands, for 1 → 3 exhibit a bathochromic shift. The thermochromic tendency of the five-coordinate complexes implies the loss of THF coordination at elevated temperatures. Finally, the electronic properties of all Ni(II) complexes were studied by time-dependent density functional theory calculations to characterize the nature of the excited states
Probing the Higgs Field Using Massive Particles as Sources and Detectors
In the Standard Model, all massive elementary particles acquire their masses
by coupling to a background Higgs field with a non-zero vacuum expectation
value. What is often overlooked is that each massive particle is also a source
of the Higgs field. A given particle can in principle shift the mass of a
neighboring particle. The mass shift effect goes beyond the usual perturbative
Feynman diagram calculations which implicitly assume that the mass of each
particle is rigidly fixed. Local mass shifts offer a unique handle on Higgs
physics since they do not require the production of on-shell Higgs bosons. We
provide theoretical estimates showing that the mass shift effect can be large
and measurable, especially near pair threshold, at both the Tevatron and the
LHC.Comment: 6 pages, no figures; Version 2 corrects some typographical errors of
factors of 2 in equations 14, 17, 18 and 19 (all of the same origin) and
mentions a linear collider as an interesting place to test the results of
this pape
Modeling atmospheric effects of the September 1859 Solar Flare
We have modeled atmospheric effects, especially ozone depletion, due to a
solar proton event which probably accompanied the extreme magnetic storm of 1-2
September 1859. We use an inferred proton fluence for this event as estimated
from nitrate levels in Greenland ice cores. We present results showing
production of odd nitrogen compounds and their impact on ozone. We also compute
rainout of nitrate in our model and compare to values from ice core data.Comment: Revised version including improved figures; Accepted for publication
in Geophys. Res. Lett, chosen to be highlighted by AG
catena-Poly[[[tetraÂkisÂ(4-methylÂpyridine-κN)copper(II)]-μ-sulfato-κ2 O:O′] 4.393-hydrate]
The structure of the title compound, {[Cu(SO4)(C6H7N)4]·4.393H2O}n, consists of Cu2+ ions surrounded in a square-planar fashion by 4-methylÂpyridine ligands, forming two crystallographically independent Cu{H3C(C5H4N)}4 units that are both located on crystallographic inversion centers. The Cu(4-methylÂpyridine)4 units are, in turn, connected with each other via bridging sulfate anions, leading to the formation of infinite [Cu{H3C(C5H4N)}4SO4]n zigzag chains along [001]. The completed coordination spheres of the Cu2+ ions are slightly distorted octaÂhedral. The axial Cu—O bonds are elongated [average length = 2.42 (4) Å] compared to the equatorial Cu—N bonds [average length = 2.043 (2) Å]. The interÂstitial space between the chains is filled with uncoordinated water molÂecules that consolidate the structure through O—H⋯O hydrogen bonding. One of the five crystallographically independent solvent water molÂecules is partially occupied with an occupancy factor of 0.396 (4). Due to hydrogen bonding between symmetry-equivalent water molÂecules across inversion centers, several of the water H atoms are disordered in 1:1 ratios over mutually exclusive positions. The crystal under investigation was found to be non-merohedrally twinned in a 0.789 (1):0.211 (1) ratio by a 180° rotation around the reciprocal b axis
Impact of Polymorphisms in PTK2 on Intrinsic Muscle Strength
Abstract Title:
Impact of Polymorphisms in PTK2 on Intrinsic Muscle Strength
Primary Presenter Full Name:
Zachary Zeller
Co-presenter Full Name(s):
Click here to enter text.
Co-author Full Name(s):
Mohamed Al-Amoodi, Whitney Jones, Danny Lee, Steven Mckenzie, Helen Miller, Seth Stubblefied, Susan Knoblach, Heather Gordish-Dressman, Dustin Hittel, Laura L. Tosi
Abstract Text (should not exceed 400 words):
Recent studies have begun to search for correlations between genetic variations and muscle strength. One such study by Stebbings et al.1 examined two single nucleotide polymorphisms (SNPs)—rs7843014 and rs7460—on the PTK2 gene. The study found that genetic variation in the PTK2 gene impacts muscle-specific force, which is the force generated per unit of cross-sectional area of muscle. Muscle-specific force ultimately represents the intrinsic strength of a muscle and is a key determinant of functional capacity and mobility. This study sought to expand on prior research by looking for associations between genetic variants of PTK2 and measures of grip strength, as well as general anthropomorphic measures, in a cohort of healthy young adults.
Our study assessed phenotypes for height, weight, VO2 max, max grip strength, and body mass index (BMI) using the Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) University of Calgary subset of 190 healthy, primarily Caucasian, individuals between the ages of 18 and 35. DNA samples were genotyped using ThermoFisher Taqman SNP genotype assays, and underwent the Applied Biosystems 7900HT real-time polymerase chain reaction (PCR) process. Analysis of covariance (ANCOVA) models were used to perform statistical analysis to look for genotype-phenotype associations.
Unlike the findings by Stebbings et al.1 an association between the PTK2 genotypes and grip strength was not found. This could be due to the lower statistical power in the grip strength test, thus potentially indicating that grip strength and muscle-specific force do not measure similar parameters of muscle strength. Genetic variation in PTK2 has also been previously associated with VO2 max, but no association was found in the current study.
Positive associations were found between genetic variants rs7843014 and rs7460 in PTK2 and BMI, and between genetic variant rs7843014 and height. High levels of functioning PTK2 have been found to have increased strength due to increased costamere density, resulting in more muscle myofibrils, and therein larger, presumably heavier muscles. However, this finding was only observed in males, and could be attributed to differential acquisition and maintenance of muscle mass based on sex.
We identified a potentially novel association between genetic variants in PTK2 and anthropomorphic phenotypes. However, we were unable to confirm the effects of genetic variants on measures of intrinsic muscle strength, namely max grip strength or VO2 max in terms of functional capacity. Further research is needed to confirm this newly identified role for PTK2
The association of polymorphism rs3736228 within the LRP5 gene with Bone Mineral Density in a Cohort of Caucasian Young Adults
INTRODUCTION: Osteoporosis is a significant burden for our aging population. Developing a better understanding of the genetic underpinnings of poor bone quality may assist in the future development of prevention strategies. Correa-Rodriguez et al. have identified a group of single nucleotide polymorphisms (SNPs) that were associated with bone mineral density (BMD) in a population of Spanish Caucasians. In particular, they found that SNP rs3736228 in the low-density lipoprotein receptor related protein 5 (LRP5) gene had an influence on BMD. While the role of LRP5 in the Wnt canonical pathway has been fairly well characterized, its association with phenotypic BMD and osteoporosis has only been explored in a limited fashion. The aim of this study is to expand on this, and to replicate the findings of previous studies in a cohort of healthy young adults.
METHODS: Cohort: The University of Calgary cohort from the Assessing Inherited Metabolic Syndrome Markers in the Young (UC AIMMY) study. Participants included consist of 168 healthy, predominantly Caucasian young adults. Phenotypes: height, weight, BMI, and total BMD. Genotyping: Allelic discrimination was determined. Statistical Analysis: After being tested for Hardy-Weinberg equilibrium (HWE), the data was run through analysis of covariance (ANCOVA).
RESULTS: Using a dominant model, we found that females with one or more copies of the risk T allele of SNP rs3736228 had a significant negative association with total BMD (p = 0.0347). However, a similar association was not seen in males in this cohort. We did not find a significant association for this polymorphism and height, weight, or BMI.
DISCUSSION: Polymorphisms in rs3736228 alter the codon in position 1330, downregulating the LRP5 cell surface receptor function. The LRP5 gene has now been shown in multiple studies to be associated with bone quality measures like calcaneal Qualitative Ultrasound (QUS) and BMD. Our study suggests that SNP rs3736228 also influences BMD in healthy young females. This supports the work of Correa-Rodriguez et al that found that when stratifying by sex, females only showed a trend towards significance (p = 0.092) in QUS measures.
SIGNIFICANCE: This study expands our understanding of the importance of LRP5 rs3736228 polymorphisms in BMD by extending its relationship to a cohort of predominantly Caucasian college students. While the development of BMD is polygenic, this work broadened the role of SNP rs3736228 across the age span, and the sexual dimorphism seen in musculoskeletal traits
Global Regulation of Nucleotide Biosynthetic Genes by c-Myc
The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis
Optical model potentials involving loosely bound p-shell nuclei around 10 MeV/A
We present the results of a search for optical model potentials for use in
the description of elastic scattering and transfer reactions involving stable
and radioactive p-shell nuclei. This was done in connection with our program to
use transfer reactions to obtain data for nuclear astrophysics, in particular
for the determination of the astrophysical S_17 factor for 7Be(p,\gamma)8B
using two (7Be,8B) proton transfer reactions. Elastic scattering was measured
using 7Li, 10B, 13C and 14N projectiles on 9Be and 13C targets at or about
E/A=10 MeV/nucleon. Woods-Saxon type optical model potentials were extracted
and are compared with potentials obtained from a microscopic double folding
model. We use these results to find optical model potentials for unstable
nuclei with emphasis on the reliability of the description they provide for
peripheral proton transfer reactions. We discuss the uncertainty introduced by
the procedure in the prediction of the DWBA cross sections for the (7Be,8B)
reactions used in extracting the astrophysical factor S_17(0).Comment: 16 pages, LaTEX file, 9 figures (PostScript files
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