Widespread environmental contamination by bisphenol A (BPA) has created the need to fully define its potential toxic mechanisms of action (MOA) to properly assess human health and ecological risks ...from exposure. Although long recognized as an estrogen receptor (ER) agonist, some data suggest that BPA may also behave as an androgen receptor (AR) antagonist. However, direct evidence of this activity is deficient. To address this knowledge gap, we employed a metabolomic approach using in vivo exposures of fathead minnows (FHM; Pimephales promelas ) to BPA either alone or in a binary mixture with 17β-trenbolone (TB), a strong AR agonist. Changes in liver metabolite profiles in female FHM in response to these exposures were determined using high resolution (1)H NMR spectroscopy and multivariate and univariate statistics. Using this approach, we observed clear evidence of the ability of BPA to mitigate the impact of TB, consistent with an antiandrogenic MOA. In addition, a transcriptional activation assay with the FHM AR was used to confirm the AR antagonistic activity of BPA in vitro. The results of these in vivo and in vitro analyses provide strong and direct evidence for ascribing an antiandrogenic MOA to BPA in vertebrates.
Abstract
The CO-to-H
2
conversion factor (
α
CO
) is central to measuring the amount and properties of molecular gas. It is known to vary with environmental conditions, and previous studies have ...revealed lower
α
CO
in the centers of some barred galaxies on kiloparsec scales. To unveil the physical drivers of such variations, we obtained Atacama Large Millimeter/submillimeter Array bands (3), (6), and (7) observations toward the inner ∼2 kpc of NGC 3627 and NGC 4321 tracing
12
CO,
13
CO, and C
18
O lines on ∼100 pc scales. Our multiline modeling and Bayesian likelihood analysis of these data sets reveal variations of molecular gas density, temperature, optical depth, and velocity dispersion, which are among the key drivers of
α
CO
. The central 300 pc nuclei in both galaxies show strong enhancement of temperature
T
k
≳ 100 K and density
n
H
2
>
10
3
cm
−3
. Assuming a CO-to-H
2
abundance of 3 × 10
−4
, we derive 4–15 times lower
α
CO
than the Galactic value across our maps, which agrees well with previous kiloparsec-scale measurements. Combining the results with our previous work on NGC 3351, we find a strong correlation of
α
CO
with low-
J
12
CO optical depths (
τ
CO
), as well as an anticorrelation with
T
k
. The
τ
CO
correlation explains most of the
α
CO
variation in the three galaxy centers, whereas changes in
T
k
influence
α
CO
to second order. Overall, the observed line width and
12
CO/
13
CO 2–1 line ratio correlate with
τ
CO
variation in these centers, and thus they are useful observational indicators for
α
CO
variation. We also test current simulation-based
α
CO
prescriptions and find a systematic overprediction, which likely originates from the mismatch of gas conditions between our data and the simulations.
The coupling test of marine atmospheric environment and tensile-compressive load for 30CrMnSiA steel was carried out with the coupling test equipment of marine atmospheric environment and tension, ...compression and bending load. The damage behavior of 30CrMnSiA steel on the coupling action of marine atmospheric environment and tensile-compressive fatigue load was discussed. The metallographic results showed that the damage behavior characteristics of static test and coupling test were consistent. The decrease of tensile strength, proof strength plastic extension and percentage elongation after fracture of 30CrMnSiA steel were accelerated by the coupling action of marine atmospheric corrosion and tensile-compressive fatigue load. And the accelerated ratio of the coupling test was more than 10 times that of the static exposure test. The fracture morphology results showed that the fracture of the coupling test was corrosion fatigue fracture, and the cracks of 30CrMnSiA steel in the coupling test extended from the fatigue source to the core, forming directional corrosion fatigue damage.
Discerning the effect of pharmacological exposures on intestinal bacterial communities in cancer patients is challenging. Here, we deconvoluted the relationship between drug exposures and changes in ...microbial composition by developing and applying a new computational method, PARADIGM (parameters associated with dynamics of gut microbiota), to a large set of longitudinal fecal microbiome profiles with detailed medication-administration records from patients undergoing allogeneic hematopoietic cell transplantation. We observed that several non-antibiotic drugs, including laxatives, antiemetics, and opioids, are associated with increased Enterococcus relative abundance and decreased alpha diversity. Shotgun metagenomic sequencing further demonstrated subspecies competition, leading to increased dominant-strain genetic convergence during allo-HCT that is significantly associated with antibiotic exposures. We integrated drug-microbiome associations to predict clinical outcomes in two validation cohorts on the basis of drug exposures alone, suggesting that this approach can generate biologically and clinically relevant insights into how pharmacological exposures can perturb or preserve microbiota composition.
The application of a computational method called PARADIGM to a large dataset of cancer patients’ longitudinal fecal specimens and detailed daily medication records reveals associations between drug exposures and the intestinal microbiota that recapitulate in vitro findings and are also predictive of clinical outcomes.
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•A computational method identifies medication-microbiome associations•Applied to the dataset of cancer patients’ fecal microbiome profiles and medication records•In silico results recapitulate in vitro measurements of anti-bacterial activities•Medication-bacteria associations are predictive of patient clinical outcomes
The application of a computational method called PARADIGM to a large dataset of cancer patients’ longitudinal fecal specimens and detailed daily medication records reveals associations between drug exposures and the intestinal microbiota that recapitulate in vitro findings and are also predictive of clinical outcomes.
Employing 2,6-bis(4S/4R)-4-phenyl-2-oxazolinylpyridine (4R/4S-Pybox) as the chiral inducing ligand, a pair of enantiopure mononuclear Dy(III) complexes, Dy(Hfac)
3
(4R/4S-Pybox) (
1R/1S
; Hfac
–
= ...1,1,1,5,5,5-hexafluoroacetylacetonate ion) have been synthesized. They are characterized by single-crystal X-ray structure analysis (ССDС nos. 2124459 (
1R
) and 2124460 (
1S
)), elemental analysis, IR spectroscopy, thermogravimetric analysis and powder X-ray diffraction. Within their mononuclear molecular structure, the Dy(III) center locates in a coordination environment afforded by a 4R/4S-Pybox ligand and three Hfac
−
ions, displaying a nine-coordinated capped square antiprism coordination geometry with
C
4v
symmetry. Solid circular dichroism spectrum further confirmed their enantiopure nature. Magnetic measurements indicated that
1R
exhibits dual magnetic relaxation behavior, which was rarely observed in chiral SIMs family. The efficient energy barrier and relaxation time for the slow relaxation process are 6.85(4) K and 2.5 × 10
−5
s, respectively.
The SVX II silicon vertex detector upgrade at CDF Antos, J.; Chao, H-Y.; Cheng, M-T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/1995, Letnik:
360, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
The SVX vertex detector has been very successful in heavy flavor physics at CDF, playing a significant role in both top and bottom analyses. SVX′, a radiation hard version of SVX, is presently taking ...data. In 1998 the Main Injector upgrade to the accelerator complex at Fermilab will provide a significant increase in luminosity, and will require a new vertex detector, SVX II. The specifications and design considerations for this detector are discussed.
Current methods to fabricate customized braces typically require a mold of the foot and often require casts to be pre-manufactured or milled from a solid block. This is time consuming and expensive. ...However, additive manufacturing opens opportunities for mass customization. Selected regions of customized protection or varying properties for the joint range of motion for braces is also possible with 3D printing solutions. This study explored the use of additive manufacturing for the mass customization of braces, using the ankle brace as an illustration. This paper showcases the methodology of using a glass scanner to obtain individual biomechanics data; incorporating personalized data in a pre-designed brace template; designing mass customized braces using Rhinoceros 6 Grasshopper; and manufacturing of the ankle brace using fused deposition modelling. Initial tests on the dynamometer showed that maximum ankle inversion angle was reduced by almost a third, as compared to barefoot conditions. This potentially will significantly reduce ankle lateral sprain injury risks at ankle inversion positions especially beyond functional range of motion and successfully demonstrated the possibility of using 3D printing solutions for similar mass customized applications.
It is unclear which patients with multiple sclerosis (MS) are most susceptible for omicron breakthrough infections.
We assessed omicron breakthrough infections in vaccinated patients with MS with and ...without disease-modifying therapies enrolled in an ongoing large prospective study. We longitudinally studied humoral responses after primary and booster vaccinations and breakthrough infections.
Omicron breakthrough infections were reported in 110/312 (36%) patients with MS, and in 105/110 (96%) infections were mild. Omicron breakthrough infections occurred more frequently in patients treated with anti-CD20 therapies and sphingosine-1 phosphate receptor (S1PR) modulators, patients with impaired humoral responses after primary immunisation (regardless of treatment) and patients without prior SARS-CoV-2 infections. After infection, antibody titres increased in patients on S1PR modulator treatment while anti-CD20 treated patients did not show an increase.
SARS-COV-2 omicron breakthrough infections are more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which correlated with decreased humoral responses after vaccination. Humoral responses after infection were higher in S1PR modulator-treated patients in comparison to patients on anti-CD20 therapies, suggesting that immunological protection from contracting infection or repeated exposures may differ between these therapies.
Ruthenium arene complexes with chalcone ligands incorporating pyridyl and anthryl units were synthesized and studied for their interaction with DNA. The binding strength of these complexes with human ...telomeric DNA was influenced by the ancillary chloro or oxalato ligands, the structure of the chalcone ligand as well as the charge of the complex.
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•Twelve ruthenium arene complexes were synthesized and studied for their interaction with DNA.•The binding strength with HTelo DNA was influenced by the nature of the ligands and the charge of the complex.
Twelve ruthenium(II) arene complexes incorporating chalcone ligands with pyridyl and anthryl units, as well as chlorido or oxalato ancillary ligands, have been synthesized and structurally characterized by 1H NMR spectroscopy, ESI mass spectrometry and elemental analysis. Compared to the oxalato compounds, the chlorido complexes were less stable and more susceptible to aquation in solution; the dissociation was suppressed in the presence of chloride ions. All six of the chlorido complexes and three of the oxalato complexes were able to bind to quadruplex DNA, exhibiting greater selectivity for HTelo over c-myc. The cationic species 3f, in which the chalcone chelates to the metal center, was found to bind to HTelo most strongly. These results indicate that the ancillary ligand, the location of the N-donor atom in the pyridyl ring, the position of the α,β-unsaturated ketone relative to the pyridyl and anthryl entities in the chalcone moiety, as well as the presence of the metal center all play significant roles in improving the binding of such complexes to quadruplex DNA.
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