Acetylation and nuclear receptor action Wang, Chenguang; Tian, Lifeng; Popov, Vladimir M. ...
The Journal of steroid biochemistry and molecular biology,
02/2011, Letnik:
123, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Acetylation is an essential post-translational modification featuring an acetyl group that is covalently conjugated to a protein substrate. Histone acetylation was first proposed nearly half a ...century ago by Dr. Vincent Allfrey. Subsequent studies have shown that the acetylated core histones are often associated with transcriptionally active chromatin. Acetylation at lysine residues of histone tails neutralizes the positive charge, which decreases their binding ability to DNA and increases the accessibility of transcription factors and coactivators to the chromatin template. In addition to histones, a number of non-histone substrates are acetylated. Acetylation of non-histone proteins governs biological processes, such as cellular proliferation and survival, transcriptional activity, and intracellular trafficking. We demonstrated that acetylation of transcription factors can regulate cellular growth. Furthermore, we showed that nuclear receptors (NRs) are acetylated at a phylogenetically conserved motif. Since our initial observations with the estrogen and androgen receptors, more than a dozen NRs have been shown to function as substrates for acetyltransferases with diverse functional consequences. This review focuses on the acetylation of NRs and the effect of acetylation on NR function. We discuss the potential role of acetylation in disease initiation and progression with an emphasis on tumorigenesis.
Introduction
The clinical impact of SARS-CoV-2 infection on human reproduction remains controversial. This prospective cohort study aimed to assess the effect of prior female SARS-CoV-2 infection on ...subsequent
in vitro
fertilization (IVF) outcomes.
Materials and methods
A total of 451 women who underwent fresh IVF treatment between December 1, 2022 and April 30, 2023 were included from an academic fertility center. Participants were divided into the infected group if they had a prior COVID-19 history before cycle initiation (n = 252), while the control group were those uninfected (n = 199). The primary outcomes were the number of oocytes retrieved and clinical pregnancy rate after fresh embryo transfer. Multivariate linear and logistic regression analyses were conducted to control for potential confounders.
Results
The number of oocytes retrieved (11.4 ± 8.3 vs. 11.6 ± 7.7; P = 0.457) and clinical pregnancy rate (70.3% vs. 73.7%; P = 0.590) were similar between infected and uninfected groups, with a fully adjusted β coefficient of 0 (95% confidence interval CI: -0.14–0.13) and odds ratio of 0.64 (95% CI: 0.20–2.07), respectively. Consistently, the two groups were comparable in cycle characteristics as well as other laboratory and pregnancy parameters. In both subgroup analyses and restricted cubic splines, different post-infection time intervals to IVF cycle initiation showed no significant associations with treatment outcomes.
Conclusion
Prior SARS-CoV-2 infection in females had no adverse influence on subsequent IVF treatment, regardless of the time interval following infection. Our findings provide reassurance for infected women planning for assisted reproduction. Additional prospective cohort studies with larger datasets and longer follow-up are required to confirm the conclusion.
Proper thymocyte development is required to establish T-cell central tolerance and to generate naive T cells, both of which are essential for T-cell homeostasis and a functional immune system. Here ...we demonstrate that the loss of transcription factor Foxp1 results in the abnormal development of T cells. Instead of generating naive T cells, Foxp1-deficient single-positive thymocytes acquire an activated phenotype prematurely in the thymus and lead to the generation of peripheral CD4+ T and CD8+ T cells that exhibit an activated phenotype and increased apoptosis and readily produce cytokines upon T-cell receptor engagement. These results identify Foxp1 as an essential transcriptional regulator for thymocyte development and the generation of quiescent naive T cells.
Observational studies have reported that
(
) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown.
A ...two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-
IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests.
IVW estimates suggested that genetically predicted anti-
IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio OR = 1.12, 95% confidence interval CI 1.01-1.24,
= 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30,
= 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64,
= 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41,
= 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis.
Our two-sample MR study demonstrated a causal relationship of
infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of
in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.
Transient receptor potential ankyrin 1 (TRPA1) is a polymodal nonselective cation channel sensitive to different physical and chemical stimuli. TRPA1 is associated with many important physiological ...functions in different species and thus is involved in different degrees of evolution. TRPA1 acts as a polymodal receptor for the perceiving of irritating chemicals, cold, heat, and mechanical sensations in various animal species. Numerous studies have supported many functions of TRPA1, but its temperature-sensing function remains controversial. Although TRPA1 is widely distributed in both invertebrates and vertebrates, and plays a crucial role in tempreture sensing, the role of TRPA1 thermosensation and molecular temperature sensitivity are species-specific. In this review, we summarize the temperature-sensing role of TRPA1 orthologues in terms of molecular, cellular, and behavioural levels.
It is widely accepted, given the complex nature of schizophrenia (SCZ) gene networks, that a few or a small number of genes are unlikely to represent the underlying functional pathways responsible ...for SCZ pathogenesis. Several studies from large cohorts have been performed to search for key SCZ network genes using different analytical approaches, such as differential expression tests, genome-wide association study (GWAS), copy number variations, and differential methylations, or from the analysis of mutations residing in the coding regions of the genome. However, only a small portion (<10%) of candidate genes identified in these studies were considered SCZ disease-associated genes in SCZ pathways. RNA sequencing (RNA-seq) has been a powerful method to detect functional signals. In this study, we used RNA-seq data from the dorsolateral prefrontal cortex (DLPFC) from 254 individuals and RNA-seq data from the amygdala region from 46 individuals. Analysis was performed using machine learning methods, including random forest and factor analysis, to prioritize the numbers of genes from previous SCZ studies. For genes most differentially expressed between SCZ and healthy controls, 18 were added to known SCZ-associated pathways. These include three genes (
, and
) for the glutamatergic synapse pathway, six genes (
, and
) for neuroactive ligand-receptor interaction, eight genes (
, and
) for the cAMP signaling pathway, and four genes (
, and
) for the dopaminergic synapse pathway. Besides the previously established pathways, 103 additional gene interactions were expanded to SCZ-associated networks, which were shared among both the DLPFC and amygdala regions. The novel knowledge of molecular targets gained from this study brings opportunities for a more complete picture of the SCZ pathogenesis. A noticeable fact is that hub genes, in the expanded networks, are not necessary differentially expressed or containing hotspots from GWAS studies, indicating that individual methods, such as differential expression tests, are not enough to identify the underlying SCZ pathways and that more integrative analysis is required to unfold the pathobiology of SCZ.
Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal ...Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in human prostate cancer. DACH1 inhibited prostate cancer cellular DNA synthesis, growth in colony forming assays, and blocked contact-independent growth in soft agar assays. DACH1 inhibited androgen receptor (AR) activity, requiring a conserved DS Domain (Dachshund domain conserved with Ski/Sno) that bound NCoR/HDAC and was recruited to an androgen-responsive gene promoter. DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. These studies show a role for the Retinal Determination Gene Network in regulating cellular growth and signaling in prostate cancer.
Background and Aims: This study are to investigate the clinical indicators of the infertile population of IVF-ET thin endometrium patients after electro-ultrasound treatment, record the observational ...data and analyze the clinical effectiveness of this treatment method. Method: Patients undergoing IVF-ET freeze-thaw embryo transfer from March 2022 to November 2022 were screened, and those who met the entry criteria were randomly grouped by random number table method. Treatment group (n=32): patients who received electro-ultrasound therapy; patients treated with electro-ultrasound (MLD-C7000) once a day for 30 minutes for 7 days for 1-3 sessions in the context of conventional FET preparation of the endothelium. Control group (n=69): Routine FET preparation of the endometrium without. Results: There were no significant differences in basic data (P > 0.05). The endometrial thickness on the day of conversion 7.75±2.00 mm was significantly higher in the treatment group than the endometrial thickness on the day of conversion 6.39±0.67 mm in the control group (P<0.05). The biochemical pregnancy rate and clinical pregnancy rate in the treatment group were higher than those in the control group, but the differences were not statistically significant (P > 0.05). Conclusion: In IVF-ET patients with thin endometrium, electro-ultrasound therapy device can effectively improve the endometrial thickness of patients with a trend of beneficial effects on clinical outcomes and can be one of the methods to improve the success rate in patients with thin endometrium. However, further increase in sample size is needed in the future to improve the accuracy of the results.
Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely ...rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-phenotype correlation in the
MSTO1
gene is rarely studied before 2017, and only 25 mutations have been described in the patients. Here, we reported two siblings with progressive cerebellar atrophy and ataxia in a Chinese family. Two compound heterozygous mutations in the
MSTO1
gene, a novel missense mutation c.571C>T (p.Arg191Trp), and a reported frameshift mutation c.1259delG (p.Gly420ValfsTer2) were identified in the patients by whole exome sequencing.
in vitro
experiments found both of the mutations lead to reduced protein abundance and link to decreased mtDNA content. Except for ataxia and delayed motor, both of the siblings also have low birth weights, learning difficulties, and dysarthria. Our report enriched the genotype and phenotype spectrums of the
MSTO1
-related disorder and supported the recessive inheritance of the disease.
•A new way to reduce blistering that the nano-channels were fabricated on the tungsten surface by FIB•The presence of " grooved surfaces " contributes to reduce blisters and inhibit the rapid growth ...of He blisters.•He-induced blistering shows a clear crystal orientation dependence.
Although tungsten is considered as one of the primary candidates for plasma-facing material (PFM) in future fusion reactors, blistering induced by plasma irradiation adversely affects fusion reactors. To overcome blistering, in this study, we proposed an approach to reduce the blistering by releasing hydrogen or helium (H/He) through the grooved surfaces of PFM. In order to verify the feasibility of this approach and the effectiveness of the transverse release of H/He, the deep grooves as the channel simulants on the tungsten surface were fabricated with different spacing using focused ion beam (FIB). The result of helium irradiation shows that the presence of grooved surfaces can reduce blisters and inhibit the rapid growth of He blisters. In addition, the blistering reduced significantly with decreasing groove spacing, especially when the groove spacing is less than 2 µm. In addition, He-induced blistering shows obvious crystal orientation dependence, and the (001) surface shows the most serious radiation damage.
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