223 research outputs found
Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome
The aim of this study was to investigate the homocysteine (Hcy) levels and the C677T polymorphism of 5,10-methyl-enetetrahydrofolate reductase (MTHFR), a crucial factor of the Hey metabolism in young women with polycystic ovary syndrome (PCOS).Seventy young women with PCOS and another 70 healthy women with low folate intake were enrolled. Cases and controls were matched for age, body mass index, and allele frequency. Hey, vitamin B(12), and folate levels were measured, and a genetic analysis of 5,10-MTHFR at nucleotide 677 was performed in all subjects.No difference in mean Hcy levels was observed between PCOS women in comparison to the control group. Considering the different MTHFR polymorphism, no significant difference was found in serum Hey levels between subjects with PCOS and controls showing CC (10.4 +/- 3.1 us. 9.7 +/- 2.9 pmol/liter +/- SD) and CT genotypes (10.9 +/- 3.8 us. 11.0 +/- 3.2 pmol/liter SD). In subjects with a TT homozygous state, a significant (P < 0.05) difference was observed between PCOS and control women (11.5 +/- 3.9 as. 22.0 +/- 7.8 pmol/liter SD).In conclusion, our data show that in PCOS women, the serum Hey levels are normal, and the C677T polymorphism of MTHFR does not influence the Hey levels like in controls
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States
The phenomena that emerge from the interaction of the stochastic opening and
closing of ion channels (channel noise) with the non-linear neural dynamics are
essential to our understanding of the operation of the nervous system. The
effects that channel noise can have on neural dynamics are generally studied
using numerical simulations of stochastic models. Algorithms based on discrete
Markov Chains (MC) seem to be the most reliable and trustworthy, but even
optimized algorithms come with a non-negligible computational cost. Diffusion
Approximation (DA) methods use Stochastic Differential Equations (SDE) to
approximate the behavior of a number of MCs, considerably speeding up
simulation times. However, model comparisons have suggested that DA methods did
not lead to the same results as in MC modeling in terms of channel noise
statistics and effects on excitability. Recently, it was shown that the
difference arose because MCs were modeled with coupled activation subunits,
while the DA was modeled using uncoupled activation subunits. Implementations
of DA with coupled subunits, in the context of a specific kinetic scheme,
yielded similar results to MC. However, it remained unclear how to generalize
these implementations to different kinetic schemes, or whether they were faster
than MC algorithms. Additionally, a steady state approximation was used for the
stochastic terms, which, as we show here, can introduce significant
inaccuracies. We derived the SDE explicitly for any given ion channel kinetic
scheme. The resulting generic equations were surprisingly simple and
interpretable - allowing an easy and efficient DA implementation. The algorithm
was tested in a voltage clamp simulation and in two different current clamp
simulations, yielding the same results as MC modeling. Also, the simulation
efficiency of this DA method demonstrated considerable superiority over MC
methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur
The Expanding Fireball of Nova Delphini 2013
A classical nova occurs when material accreting onto the surface of a white
dwarf in a close binary system ignites in a thermonuclear runaway. Complex
structures observed in the ejecta at late stages could result from interactions
with the companion during the common envelope phase. Alternatively, the
explosion could be intrinsically bipolar, resulting from a localized ignition
on the surface of the white dwarf or as a consequence of rotational distortion.
Studying the structure of novae during the earliest phases is challenging
because of the high spatial resolution needed to measure their small sizes.
Here we report near-infrared interferometric measurements of the angular size
of Nova Delphini 2013, starting from one day after the explosion and continuing
with extensive time coverage during the first 43 days. Changes in the apparent
expansion rate can be explained by an explosion model consisting of an
optically thick core surrounded by a diffuse envelope. The optical depth of the
ejected material changes as it expands. We detect an ellipticity in the light
distribution, suggesting a prolate or bipolar structure that develops as early
as the second day. Combining the angular expansion rate with radial velocity
measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc
from the Sun.Comment: Published in Nature. 32 pages. Final version available at
http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm
Validation of techniques to mitigate copper surface contamination in CUORE
In this article we describe the background challenges for the CUORE
experiment posed by surface contamination of inert detector materials such as
copper, and present three techniques explored to mitigate these backgrounds.
Using data from a dedicated test apparatus constructed to validate and compare
these techniques we demonstrate that copper surface contamination levels better
than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels
are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit
on the number of background counts in the region of interest is 0.02-0.03
counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table
Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome
Synthesis and Electronic Structure Determination of Uranium(VI) Ligand Radical Complexes
Pentagonal bipyramidal uranyl complexes of salen ligands, N,N’-bis(3-tert-butyl-(5R)-salicylidene)-1,2-phenylenediamine, in which R = tBu (1a), OMe (1b), and NMe2 (1c), were prepared and the electronic structure of the one-electron oxidized species [1a-c]+ were investigated in solution. The solid-state structures of 1a and 1b were solved by X-ray crystallography, and in the case of 1b an asymmetric UO22+ unit was found due to an intermolecular hydrogen bonding interaction. Electrochemical investigation of 1a-c by cyclic voltammetry showed that each complex exhibited at least one quasi-reversible redox process assigned to the oxidation of the phenolate moieties to phenoxyl radicals. The trend in redox potentials matches the electron-donating ability of the para-phenolate substituents. The electron paramagnetic resonance spectra of cations [1a-c]+ exhibited gav values of 1.997, 1.999, and 1.995, respectively, reflecting the ligand radical character of the oxidized forms, and in addition, spin-orbit coupling to the uranium centre. Chemical oxidation as monitored by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy afforded the one-electron oxidized species. Weak low energy intra-ligand charge transfer (CT) transitions were observed for [1a-c]+ indicating localization of the ligand radical to form a phenolate / phenoxyl radical species. Further analysis using density functional theory (DFT) calculations predicted a localized phenoxyl radical for [1a-c]+ with a small but significant contribution of the phenylenediamine unit to the spin density. Time-dependent DFT (TD-DFT) calculations provided further insight into the nature of the low energy transitions, predicting both phenolate to phenoxyl intervalence charge transfer (IVCT) and phenylenediamine to phenoxyl CT character. Overall, [1a-c]+ are determined to be relatively localized ligand radical complexes, in which localization is enhanced as the electron donating ability of the para-phenolate substituents is increased (NMe2 > OMe > tBu)
State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)
PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy
Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome
Objective: this study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. Materials and methods: DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. Results: the distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Conclusion: our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins
Search for 14.4 keV Solar Axions from M1 Transition of 57Fe with CUORE Crystals
We report the results of a search for axions from the 14.4 keV M1 transition from 57Fe in the core of the sun using the axio-electric effect in TeO2bolometers. The detectors are 5
× 5 × 5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg⋅d of data was made using a newly developed low energy trigger which was optimized to reduce the energy threshold of the detector. An upper limit of 0.58 c⋅kg−1⋅d−1 is established at 95% C.L., which translates into lower bounds fA ≥ 3.12 × 105 GeV 95% C.L. (DFSZ model) and fA ≥ 2.41 × 104 GeV 95% C.L. (KSVZ model) on the Peccei-Quinn symmetry-breaking scale, for a value of S = 0.5 of the flavor-singlet axial vector matrix element. These bounds can be expressed in terms of axion masses as mA ≤ 19.2 eV and mA ≤ 250 eV at 95% C.L. in the DFSZ and KSVZ models respectively. Bounds are given also for the interval 0.35 ≤ S ≤ 0.55
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