This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the ...spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.
A
bstract
We address the nonperturbative calculation of the inclusive decay rate of semileptonic
B
(
s
)
-meson decays from lattice QCD. Precise Standard-Model predictions are key ingredients in ...searches for new physics, and this type of computation may eventually provide new insight into the long-standing tension between the inclusive and exclusive determinations of the Cabibbo-Kobayashi-Maskawa (CKM) matrix elements |
V
cb
| and |
V
ub
|. We present results from a pilot lattice computation for
B
s
→
X
c
lν
l
, where the initial
b
quark described by the relativistic-heavy-quark (RHQ) formalism on the lattice and the other valence quarks discretised with domain-wall fermions are simulated approximately at their physical quark masses. We compare two different methods for computing the decay rate from lattice data of Euclidean
n
-point functions, namely Chebyshev and Backus-Gilbert approaches. We further study how much the ground-state meson dominates the inclusive decay rate and indicate our strategy towards a computation with a more comprehensive systematic error budget.
Significance Seeds are complex structures that are comprised of the embryo, endosperm, and seed coat. Despite their importance for food, fiber, and fuel, the cellular processes that characterize ...different regions of the seed are not known. We profiled gene activity genome-wide in every organ, tissue, and cell type of Arabidopsis seeds from fertilization through maturity. The resulting mRNA datasets provide unique insights into the cellular processes that occur in understudied seed regions, revealing unexpected overlaps in the functional identities of seed regions and enabling predictions of gene regulatory networks. This dataset is an essential resource for studies of seed biology.
Imprinted genes are expressed primarily or exclusively from either the maternal or paternal allele, a phenomenon that occurs in flowering plants and mammals. Flowering plant imprinted gene expression ...has been described primarily in endosperm, a terminal nutritive tissue consumed by the embryo during seed development or after germination. Imprinted expression in Arabidopsis thaliana endosperm is orchestrated by differences in cytosine DNA methylation between the paternal and maternal genomes as well as by Polycomb group proteins. Currently, only 11 imprinted A. thaliana genes are known. Here, we use extensive sequencing of cDNA libraries to identify 9 paternally expressed and 34 maternally expressed imprinted genes in A. thaliana endosperm that are regulated by the DNA-demethylating glycosylase DEMETER, the DNA methyltransferase MET1, and/or the core Polycomb group protein FIE. These genes encode transcription factors, proteins involved in hormone signaling, components of the ubiquitin protein degradation pathway, regulators of histone and DNA methylation, and small RNA pathway proteins. We also identify maternally expressed genes that may be regulated by unknown mechanisms or deposited from maternal tissues. We did not detect any imprinted genes in the embryo. Our results show that imprinted gene expression is an extensive mechanistically complex phenomenon that likely affects multiple aspects of seed development.
Objectives
Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We ...hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF‐β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.
Methods
In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF‐β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real‐time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre‐injury day 5 to post‐injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.
Results
TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF‐β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF‐β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.
Conclusions
TAM has antifibrotic potential via the regulation of TGF‐β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.
Level of Evidence
NA Laryngoscope, 133:2248–2254, 2023
This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention.
Abstract High-spatial-resolution observations of CO isotopologue line emission in protoplanetary disks at mid-inclinations (≈30°–75°) allow us to characterize the gas structure in detail, including ...radial and vertical substructures, emission surface heights and their dependencies on source characteristics, and disk temperature profiles. By combining observations of a suite of CO isotopologues, we can map the two-dimensional ( r , z ) disk structure from the disk upper atmosphere, as traced by CO, to near the midplane, as probed by less abundant isotopologues. Here, we present high-angular-resolution (≲0.″1 to ≈0.″2; ≈15–30 au) observations of CO, 13 CO, and C 18 O in either or both J = 2–1 and J = 3–2 lines in the transition disks around DM Tau, Sz 91, LkCa 15, and HD 34282. We derived line emission surfaces in CO for all disks and in 13 CO for the DM Tau and LkCa 15 disks. With these observations, we do not resolve the vertical structure of C 18 O in any disk, which is instead consistent with C 18 O emission originating from the midplane. Both the J = 2–1 and J = 3–2 lines show similar heights. Using the derived emission surfaces, we computed radial and vertical gas temperature distributions for each disk, including empirical temperature models for the DM Tau and LkCa 15 disks. After combining our sample with literature sources, we find that 13 CO line emitting heights are also tentatively linked with source characteristics, e.g., stellar host mass, gas temperature, disk size, and show steeper trends than seen in CO emission surfaces.
The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence ...suggests that VCAN is an important target of chromosomal
gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis (
< 0.001) and worse 5-year overall survival after radical nephrectomy (
= 0.014).
, VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such as
, and
Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies.
This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer.
.
OBJECTIVESVocal fold scar remains a therapeutic challenge. Vocal fold fibroblasts (VFFs) secrete extracellular matrix (ECM), and transforming growth factor-beta 1 (TGF-β1)-mediated fibroblast to ...myofibroblast differentiation is central to the development of fibrosis. The transient receptor potential (TRP) channel superfamily is a group of nonselective cation channels, and activation of TRP ankyrin 1 (TRPA1) channel has been shown to have antifibrotic effects through TGF-β1/Smad signaling in various organs. This study aimed to elucidate expression of TRPA1 and the impact of TRPA1 activation on TGF-β1/Smad signaling in VFFs.METHODSVocal folds were dissected from 10-week-old, male Sprague-Dawley rats and primary VFFs were established. TRPA1 was examined in VFFs and lamina propria via immunostaining. VFFs were treated with allyl isothiocyanate (AITC, TRP channel agonist, 10-5 M) ± TGF-β1 (10 ng/ml) ± A-967079 (selective TRPA1 channel antagonist, 5.0 × 10-7 M) for 4 or 24 h. Trpa1, Smad3, Smad7, Col1a1, Acta2, and Has1 mRNA expression were quantified via qPCR.RESULTSTRPA1 was expressed in cultured VFFs and the lamina propria. TGF-β1 administration significantly increased Trpa1 compared to control. AITC alone did not alter Smad3, Smad7, Acta2, or ECM related genes. However, the combination of AITC and TGF-β1 significantly increased Smad3 and decreased Smad7 and Acta2 compared to TGF-β1 alone; A-967079 significantly reduced this response.CONCLUSIONSVFFs expressed TRPA1, and the activation of TRPA1 regulated TGF-β1/Smad signaling in VFFs. These findings provide preliminary insights into potential anti-fibrotic mechanisms of TRPA1 activation through TGF-β1/Smad signaling in VFFs.LEVEL OF EVIDENCENA Laryngoscope, 2024.
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