Abstract
Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. Anaplastic thyroid cancer (ATC) is highly aggressive, ...dedifferentiated, and patients have a median survival of fewer than 6 months. Oncogenic alterations in ATC include aberrant phosphoinositide 3 kinase (PI3K) signaling through receptor tyrosine kinase (RTK) amplification, loss of phosphoinositide phosphatase expression and function, and protein kinase B (Akt) amplification. Furthermore, the loss of expression of the tumor suppressor thyroid hormone receptor beta (TRβ) is strongly associated with ATC. TRβ is known to suppress PI3K in follicular thyroid cancer and breast cancer by binding to the PI3K regulatory subunit p85α. However, the role of TRβ in suppressing PI3K signaling in ATC is not completely delineated. Here we report that TRβ indeed suppresses PI3K signaling in ATC cell lines through unreported genomic mechanisms, including a decrease in RTK expression and an increase in phosphoinositide and Akt phosphatase expression. Furthermore, the reintroduction and activation of TRβ in ATC cell lines enables an increase in the efficacy of the competitive PI3K inhibitors LY294002 and buparlisib on cell viability, migration, and suppression of PI3K signaling. These findings not only uncover additional tumor suppressor mechanisms of TRβ but shed light on the implication of TRβ status and activation on inhibitor efficacy in ATC tumors.
Metastatic breast cancer is refractory to conventional therapies and is an end-stage disease. RUNX2 is a transcription factor that becomes oncogenic when aberrantly expressed in multiple tumor types, ...including breast cancer, supporting tumor progression and metastases. Our previous work demonstrated that the thyroid hormone receptor beta (TRβ)
inhibits
RUNX2 expression and tumorigenic characteristics in thyroid cells. As TRβ is a tumor suppressor, we investigated the compelling question whether TRβ also regulates RUNX2 in breast cancer. The Cancer Genome Atlas indicates that TRβ expression is decreased in the most aggressive basal-like subtype of breast cancer. We established that modulated levels of TRβ results in corresponding changes in the high levels of RUNX2 expression in metastatic, basal-like breast cells. The MDA-MB-231 triple-negative breast cancer cell line exhibits low expression of TRβ and high levels of RUNX2. Increased expression of TRβ decreased RUNX2 levels. The thyroid hormone-mediated suppression of RUNX2 is TRβ specific as TRα overexpression failed to alter RUNX2 expression. Consistent with these findings, knockdown of TRβ in non-tumor MCF10A mammary epithelial-like cells results in an increase in RUNX2 and RUNX2 target genes. Mechanistically, TRβ directly interacts with the proximal promoter of RUNX2 through a thyroid hormone response element to reduce promoter activity. The TRβ suppression of the oncogene RUNX2 is a signaling pathway shared by thyroid and breast cancers. Our findings provide a novel mechanism for TRβ-mediated tumor suppression in breast cancers. This pathway may be common to many solid tumors and impact treatment for metastatic cancers.
Galaxies with stellar masses near M* contain the majority of stellar mass in the universe, and are therefore of special interest in the study of galaxy evolution. The Milky Way (MW) and Andromeda ...(M31) have present-day stellar masses near M*, at 5 x 10 super(10) M sub(middot in circle) (defined here to be MW-mass) and 10 super(11) M sub(middot in circle) (defined to be M31-mass). We study the typical progenitors of these galaxies using the FOURSTAR Galaxy Evolution Survey (ZFOURGE). ZFOURGE is a deep medium-band near-IR imaging survey, which is sensitive to the progenitors of these galaxies out to z ~ 3. We use abundance-matching techniques to identify the main progenitors of these galaxies at higher redshifts. We measure the evolution in the stellar mass, rest-frame colors, morphologies, far-IR luminosities, and star formation rates, combining our deep multiwavelength imaging with near-IR Hubble Space Telescope imaging from Cosmic Near-IR Deep Extragalactic Legacy Survey (CANDELS), and Spitzer and Herschel far-IR imaging from Great Observatories Origins Deep Survey-Herschel and CANDELS-Herschel. The typical MW-mass and M31-mass progenitors passed through the same evolution stages, evolving from blue, star-forming disk galaxies at the earliest stages to redder dust-obscured IR-luminous galaxies in intermediate stages and to red, more quiescent galaxies at their latest stages. The progenitors of the MW-mass galaxies reached each evolutionary stage at later times (lower redshifts) and with stellar masses that are a factor of two to three lower than the progenitors of the M31-mass galaxies. The process driving this evolution, including the suppression of star formation in present-day M* galaxies, requires an evolving stellar-mass/halo-mass ratio and/or evolving halo-mass threshold for quiescent galaxies. The effective size and SFRs imply that the baryonic cold-gas fractions drop as galaxies evolve from high redshift to z ~ 0 and are strongly anticorrelated with an increase in the Sersic index. Therefore, the growth of galaxy bulges in M* galaxies corresponds to a rapid decline in the galaxy gas fractions and/or a decrease in the star formation efficiency.
Abstract
Background
Low bone mineral density (BMD) in inflammatory bowel disease (IBD) is multifactorial and includes nutritional status. The study aimed to look for the association between fat body ...mass and fat-free mass and BMD of the lumbar spine (L1-L4), femoral neck and total body.
Methods
The study subjects included 95 patients with Crohn’s disease (CD), 68 with ulcerative colitis (UC) and 40 healthy adults (control group - CG) in age of 18-50 years old, recruited at the Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences between 2020-2021. The summary of the methods is presented in Figure 1.
DXA- Dual-energy X-ray absorptiometry
Results
A lowered fat mass percentage occurred in about 8% of CD, 13% of UC and 3% of CG. Additionally, an increased percentage of fat mass occurred above 50% of CD, 40% of UC and about 60% of CG. It is interesting because the median, lower and upper quartile for BMI (body mass index) was normal for CD 21.70 (19.20; 24.40 and UC 20.30 (18.45; 24.05). Fat body mass and fat mass percentage were significantly lower among UC compared with the CG and CD in women but not men. Additionally, healthy women presented higher fat-free mass than CD and UC women. We did not find the same differences for men. In CD women, but not men, with a high body fat percentage, we find a higher BMD and T-score of L1-L4-but than the standard body fat percentage. Fat body mass correlated positively with BMD and T-score of L1-L4 and total body in men with UC but not in men with CD and women with UC. However, we find a positive correlation between fat body mass and BMD and T-score of L1-L4, femoral neck and total body. Among CG, positive correlations occurred between the fat body mass and BMD of L1-L4, BMD of total body and T-score of total body, but only in men. Fat-free mass correlated positively with BMD and T-score of L1-L4 and total body and BMD, T-score and Z-score of the femoral neck in CD women but not UC women. In men, correlations occurred between the fat-free mass and BMD and T-score of L1-L4, femoral neck and total body in CD. Among UC, fat-free mass correlated with BMD, T-score, and Z-score of L1-L4, femoral neck and total body. We did not find a correlation in CG. CRP (C-reactive protein) correlated negatively with fat body mass only in men with CD and negatively in healthy women.
Conclusion
A higher fat mass percentage is common among IBD patients and healthy adults despite normal BMI. Probably, fat body mass and fat-free mass are predictors of nutritional status and the course of the disease, therefore correlated positively with BMD, T-score and Z-score. On the other hand, a high-fat mass percentage with a normal BMI indicates metabolic obesity with normal weight.
A measurement of the K+→ π+μ+μ− decay Cortina Gil, E.; Kleimenova, A.; Minucci, E. ...
The journal of high energy physics,
11/2022, Letnik:
2022, Številka:
11
Journal Article
Recenzirano
Odprti dostop
A
bstract
A sample of 2
.
8 × 10
4
K
+
→
π
+
μ
+
μ
−
candidates with negligible background was collected by the NA62 experiment at the CERN SPS in 2017–2018. The model-independent branching fraction ...is measured to be (9
.
15 ± 0
.
08) × 10
−
8
, a factor three more precise than previous measurements. The decay form factor is presented as a function of the squared dimuon mass. A measurement of the form factor parameters and their uncertainties is performed using a description based on Chiral Perturbation Theory at
O
(
p
6
).
The first search for ultra-rare K+ decays into the π+e+e−e+e− final state is reported, using a dataset collected by the NA62 experiment at CERN in 2017–2018. An upper limit of 1.4×10−8 at 90% CL is ...obtained for the branching ratio of the K+→π+e+e−e+e− decay, predicted in the Standard Model to be (7.2±0.7)×10−11. Upper limits at 90% CL are obtained at the level of 10−9 for the branching ratios of two prompt decay chains involving pair-production of hidden-sector mediators: K+→π+aa, a→e+e− and K+→π+S, S→A′A′, A′→e+e−.
The European Aerosol Research Lidar Network (EARLINET), part of the Aerosols, Clouds and Trace gases Research Infrastructure (ACTRIS), organized an intensive observational campaign in May 2020, with ...the objective of monitoring the atmospheric state over Europe during the COVID-19 lockdown and relaxation period. Besides the standard operational processing of the lidar data in EARLINET, for seven EARLINET sites having collocated sun-photometric observations in the Aerosol Robotic Network (AERONET), a network exercise was held in order to derive profiles of the concentration and effective column size distributions of the aerosols in the atmosphere, by applying the GRASP/GARRLiC (from Generalized Aerosol Retrieval from Radiometer and Lidar Combined data – GARRLiC – part of the Generalized Retrieval of Atmosphere and Surface Properties – GRASP) inversion algorithm. The objective of this network exercise was to explore the possibility of identifying the anthropogenic component and of monitoring its spatial and temporal characteristics in the COVID-19 lockdown and relaxation period. While the number of cases is far from being statistically significant so as to provide a conclusive description of the atmospheric aerosols over Europe during this period, this network exercise was fundamental to deriving a common methodology for applying GRASP/GARRLiC to a network of instruments with different characteristics. The limits of the approach are discussed, in particular the missing information close to the ground in the lidar measurements due to the instrument geometry and the sensitivity of the GRASP/GARRLiC retrieval to the settings used, especially for cases with low aerosol optical depth (AOD) like the ones we show here. We found that this sensitivity is well-characterized in the GRASP/GARRLiC products, since it is included in their retrieval uncertainties.
A
bstract
The NA62 experiment at CERN, designed to study the ultra-rare decay
K
+
→
π
+
ν
ν
¯
, has also collected data in beam-dump mode. In this configuration, dark photons may be produced by ...protons dumped on an absorber and reach a decay volume beginning 80 m downstream. A search for dark photons decaying in flight to
μ
+
μ
−
pairs is reported, based on a sample of 1
.
4 × 10
17
protons on dump collected in 2021. No evidence for a dark photon signal is observed. A region of the parameter space is excluded at 90% CL, improving on previous experimental limits for dark photon masses between 215 and 550 MeV
/c
2
.
Human genomic clones that span the entire protein S expressed gene (PS alpha) and the 3' two-thirds of the protein S pseudogene (PS beta) have been isolated and characterized. The PS alpha gene is ...greater than 80 kilobases in length and contains 14 introns and 15 exons, as well as 6 repetitive "Alu" sequences. Exons I and XV contain 112 and 1139 bp 5' and 3' noncoding segments in addition to the amino and carboxyl termini, respectively. Exons I-VIII encode protein segments that are homologous to the vitamin K dependent clotting proteins and are bounded by introns whose position and type are identical with other members of this protein family. Exons IX-XV encode protein segments homologous to sex hormone binding globulin (SHBG) and are bounded by introns of identical type and position as in the SHBG gene. Genomic clones for the PS beta gene cover a distance of greater than 55 kilobases and contain segments corresponding to amino acids 46-635 of the mature protein and the 1.1-kb 3' noncoding region of the cDNA. The presence of multiple base changes in the coding portions of this gene, resulting in termination codons and frame shifts, suggests that it is a pseudogene. Comparison of DNA sequences for the two genes reveals 97% identity for coding and 3' noncoding, and 95.4% for intronic regions, suggesting divergence of the two genes is a relatively recent event.
Searches for lepton number violating K+→π−e+e+ and K+→π−π0e+e+ decays have been performed using the complete dataset collected by the NA62 experiment at CERN in 2016–2018. Upper limits of 5.3×10−11 ...and 8.5×10−10 are obtained on the decay branching fractions at 90% confidence level. The former result improves by a factor of four over the previous best limit, while the latter result represents the first limit on the K+→π−π0e+e+ decay rate.
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