Polymethyl methacrylate (PMMA)-made prostheses used in the oral cavity were evaluated by multimodal assessment in order to elucidate the biodeterioration of PMMA. In used dentures (UD), the ...micro-Vickers hardness of the polished denture surface and denture basal surface was lower than that of the torn surface (p<0.05), whereas the shaved surface approximately 100 µm from the polished surface showed a similar value to the torn surface. By contrast, there were no differences among these surfaces in new resin (NR). The volatile content of UD was higher than that of NR (p<0.05). Component analysis by ATR-FTIR showed specific spectra (1,700–1,400 cm−1) only in UD. This study revealed that PMMA deteriorated during long-term use in the oral cavity in terms of hardness and volatile content with component alteration, and suggests the involvement of biodeterioration, possibly due to saliva and oral microbiota.
Abstract
We present new observations with the Atacama Large Millimeter/submillimeter Array for a gravitationally lensed galaxy at
z
= 9.1, MACS1149-JD1. O
iii
88
μ
m emission is detected at 10
σ
...with a spatial resolution of ∼0.3 kpc in the source plane, enabling the most distant morphokinematic study of a galaxy. The O
iii
emission is distributed smoothly without any resolved clumps and shows a clear velocity gradient with Δ
V
obs
/2
σ
tot
= 0.84 ± 0.23, where Δ
V
obs
is the observed maximum velocity difference and
σ
tot
is the velocity dispersion measured in the spatially integrated line profile, suggesting a rotating system. Assuming a geometrically thin self-gravitating rotation disk model, we obtain
V
rot
/
σ
V
=
0.67
−
0.26
+
0.73
, where
V
rot
and
σ
V
are the rotation velocity and velocity dispersion, respectively, still consistent with rotation. The resulting disk mass of
0.65
−
0.40
+
1.37
×
10
9
M
⊙
is consistent with being associated with the stellar mass identified with a 300 Myr old stellar population independently indicated by a Balmer break in the spectral energy distribution. We conclude that the most of the dynamical mass is associated with the previously identified mature stellar population that formed at
z
∼ 15.
Background:There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In ...this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events.Conclusions:In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.
Abstract
We present the results of 300 pc resolution Atacama Large Millimeter/submillimeter Array imaging of the O
iii
88 μm line and dust continuum emission from a
z
= 8.312 Lyman-break galaxy ...MACS0416_Y1. The velocity-integrated O
iii
emission has three peaks that are likely associated with three young stellar clumps of MACS0416_Y1, while the channel map shows a complicated velocity structure with little indication of a global velocity gradient unlike what was found in C
ii
158 μm at a larger scale, suggesting random bulk motion of ionized gas clouds inside the galaxy. In contrast, dust emission appears as two individual clumps apparently separating or bridging the O
iii
/stellar clumps. The cross-correlation coefficient between dust and ultraviolet-related emission (i.e., O
iii
and ultraviolet continuum) is unity on a galactic scale, while it drops at <1 kpc, suggesting well-mixed geometry of multiphase interstellar media on subkiloparsec scales. If the cutoff scale characterizes different stages of star formation, the cutoff scale can be explained by gravitational instability of turbulent gas. We also report on a kiloparsec-scale off-center cavity embedded in the dust continuum image. This could be a superbubble producing galactic-scale outflows, since the energy injection from the 4 Myr starburst suggested by a spectral energy distribution analysis is large enough to push the surrounding media creating a kiloparsec-scale cavity.
Abstract
We present updated measurements of the O
iii
88
μ
m, C
ii
158
μ
m, and dust continuum emission from a star-forming galaxy at
z
= 7.212, SXDF-NB1006-2, by utilizing Atacama Large ...Millimeter/submillimeter Array (ALMA) archival data sets analysed in previous studies and data sets that have not been analysed before. The follow-up ALMA observations with higher angular resolution and sensitivity reveal a clumpy structure of the O
iii
emission on a scale of 0.32–0.85 kpc. We also combined all the ALMA O
iii
(C
ii
) data sets and updated the O
iii
(C
ii
) detection to 5.9
σ
(3.6
σ
–4.5
σ
). The non-detection of C
ii
with data from the REBELS large program implies the incompleteness of spectral-scan surveys using C
ii
to detect galaxies with high star formation rates (SFRs) but marginal C
ii
emission at high-
z
. The dust continuum at 90 and 160
μ
m remains undetected, indicating little dust content of <3.9 × 10
6
M
⊙
(3
σ
), and we obtained a more stringent constraint on the total infrared luminosity. We updated the O
iii
/C
ii
luminosity ratios to 10.2 ± 4.7 (6.1 ± 3.5) and 20 ± 12 (9.6 ± 6.1) for the 4.5
σ
and 3.6
σ
C
ii
detections, respectively, where the ratios in the parentheses are corrected for the surface brightness dimming effect on the extended C
ii
emission. We also found a strong C
ii
deficit (0.6–1.3 dex) between SXDF-NB1006-2 and the mean
L
C
II
−SFR relation of galaxies at 0 <
z
< 9.
The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to ...deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH. We identified the A3A ssDNA binding motif as (T/C)TC(A/G), which correlated with enzymatic activity. We also validated that A3A binds RNA in a sequence specific manner. A3A bound tighter to substrate binding motif within a hairpin loop compared to linear oligonucleotide, suggesting A3A affinity is modulated by substrate structure. Based on these findings and previously published A3A-ssDNA co-crystal structures, we propose a new model with intra-DNA interactions for the molecular mechanism underlying A3A sequence preference. Overall, the sequence and structural preferences identified for A3A leads to a new paradigm for identifying A3A's involvement in mutation of endogenous or exogenous DNA.
Mutations in WNK kinases cause the human hypertensive disease pseudohypoaldosteronism type II (PHAII), but the regulatory mechanisms of the WNK kinases are not well understood. Mutations in ...kelch-like 3 (KLHL3) and Cullin3 were also recently identified as causing PHAII. Therefore, new insights into the mechanisms of human hypertension can be gained by determining how these components interact and how they are involved in the pathogenesis of PHAII. Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level. The reduced interaction of KLHL3 and WNK4 by PHAII-causing mutations in either protein reduced the ubiquitination of WNK4, resulting in an increased level of WNK4 protein. Transgenic mice overexpressing WNK4 showed PHAII phenotypes, and WNK4 protein was indeed increased in Wnk4D561A/+ PHAII model mice. Thus, WNK4 is a target for KLHL3-mediated ubiquitination, and the impaired ubiquitination of WNK4 is a common mechanism of human hereditary hypertension.
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► WNK4 kinase is a substrate of KLHL3-Cullin3-targeted ubiquitination ► PHAII-causing mutations of WNK4, KLHL3, and Cullin3 decrease WNK4 ubiquitination ► Impaired WNK4 ubiquitination activates the OSR1/SPAK-NCC axis and causes hypertension
Mutations in WNK kinases cause the human hypertensive disease pseudohypoaldosteronism type II (PHAII). Mutations in kelch-like 3 (KLHL3) and Cullin3 were also recently identified as causing PHAII. Therefore, new insights into the mechanisms of human hypertension can be gained by determining how these components interact and how they are involved in the pathogenesis of PHAII. Here, Uchida and colleagues found that WNK4 is a target for KLHL3-Cullin3-mediated ubiquitination and that the dysregulation of WNK4 ubiquitination is a molecular mechanism of human hypertension.
APOBEC3 proteins (A3s) are enzymes that catalyze the deamination of cytidine to uridine in single-stranded DNA (ssDNA) substrates, thus playing a key role in innate antiviral immunity. However, ...the APOBEC3 family has also been linked to many mutational signatures in cancer cells, which has led to an intense interest to develop inhibitors of A3's catalytic activity as therapeutics as well as tools to study A3's biochemistry, structure, and cellular function. Recent studies have shown that ssDNA containing 2'-deoxy-zebularine (dZ-ssDNA) is an inhibitor of A3s such as A3A, A3B, and A3G, although the atomic determinants of this activity have remained unknown. To fill this knowledge gap, we determined a 1.5 Å resolution structure of a dZ-ssDNA inhibitor bound to active A3G. The crystal structure revealed that the activated dZ-H
O mimics the transition state by coordinating the active site Zn
and engaging in additional stabilizing interactions, such as the one with the catalytic residue E259. Therefore, this structure allowed us to capture a snapshot of the A3's transition state and suggests that developing transition-state mimicking inhibitors may provide a new opportunity to design more targeted molecules for A3s in the future.
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