2,989 research outputs found
Functionalization of polyurethanes by incorporation of alkyne side-groups to oligodiols and subsequent thiol-yne post-modification
Nano-nutrition of chicken embryos. The effect of silver nanoparticles and glutamine on molecular responses, and the morphology of pectoral muscle:the effect of silver nanoparticles and glutamine on molecular responses, and the morphology of pectoral muscle
The RNA-binding landscape of HAX1 protein indicates its involvement in translation and ribosome assembly
HAX1 is a human protein with no known homologues or structural domains. Mutations in the HAX1 gene cause severe congenital neutropenia through mechanisms that are poorly understood. Previous studies reported the RNA-binding capacity of HAX1, but the role of this binding in physiology and pathology remains unexplained. Here, we report the transcriptome-wide characterization of HAX1 RNA targets using RIP-seq and CRAC, indicating that HAX1 binds transcripts involved in translation, ribosome biogenesis, and rRNA processing. Using CRISPR knockouts, we find that HAX1 RNA targets partially overlap with transcripts downregulated in HAX1 KO, implying a role in mRNA stabilization. Gene ontology analysis demonstrated that genes differentially expressed in HAX1 KO (including genes involved in ribosome biogenesis and translation) are also enriched in a subset of genes whose expression correlates with HAX1 expression in four analyzed neoplasms. The functional connection to ribosome biogenesis was also demonstrated by gradient sedimentation ribosome profiles, which revealed differences in the small subunit:monosome ratio in HAX1 WT/KO. We speculate that changes in HAX1 expression may be important for the etiology of HAX1-linked diseases through dysregulation of translation
Dietary macronutrients and fluid intakes in a sample of pregnant women with either gestational diabetes or type 1 diabetes mellitus, assessed in comparison with Polish nutritional guidelines
Objectives: Pregnancy is a critical period during which environmental factors such as nutrition can affect development. Maintaining proper nutrition becomes even more significant when pregnant women have diabetes. The aim of this study was to measure changes in energy and macronutrient intakes among pregnant women and patients diagnosed either with gestational diabetes mellitus (GDM) during pregnancy, or, type 1 diabetes mellitus (T1DM) before pregnancy, and to assess the pregnant women’s dietary intakes in comparison with Polish Institute of Food and Nutrition nutritional guidelines.Material and methods: The analysis was conducted among 83 pregnant women (29 GDM patients, 26 T1DM patients and 28 normal pregnancy patients — the control group) from whom we gathered nutritional data during the second part of their pregnancies. Data on each woman’s diet during pregnancy was collected is self-completed dietary records during seven consecutive 24-hour periods.Results: The mean macronutrient intake of the GDM patients was 32.1% fat, 19.5% protein, and 48.3% carbohydrates; in the T1DM group the results were 34.2%, 19.4% and 46.4% respectively; and in control group they were 31.8%, 17.6% and 50.5% respectively. This study showed that many of the pregnant women did not reach the recommended level of energy intake during pregnancy. Moreover, most of the women exceeded their fat requirements, and fat intake as a proportion of energy intakes also exceeded the guidelines in more than 60% of the women across all groups.Conclusions: The implications and possible causes of excessive fat intake during pregnancy and pregnancies complicated by diabetes are underestimated and undertreated by obstetricians and warrant further investigation, especially in association with gestational weight gain, maternal and fetal perinatal complications, and post-gestational diabetes
Dietary vitamin and mineral intakes in a sample of pregnant women with either gestational diabetes or type 1 diabetes mellitus, assessed in comparison with Polish nutritional guidelines
Objectives: Maintaining proper nutrition during pregnancy is crucial for pregnant women and especially for who havebeen diagnosed with type 1 diabetes mellitus (T1DM) or who develop gestational diabetes mellitus (GDM).Material and methods: To measure differences in vitamin and mineral intakes among women with normal pregnancies,pregnant women with GDM, and pregnant women with pre-gestational T1DM; and to assess the women’s dietary intakes in comparison with Polish nutritional guidelines. The analysis was conducted among 83 pregnant women (29 GDM patients, 26 T1DM patients and 28 normal pregnancy participants) from whom we collected seven-day 24-hour dietary records during the second part of their pregnancies.Results: There were no statistically significant differences observed for most of the vitamin and mineral intakes across the three groups. However, we did observe a significant difference in the vitamin C and calcium intakes between groups. The mean vitamin C and calcium intakes were significantly higher in the control group than among the diabetic patients. Insufficient dietary calcium intakes were found among 52.3% of the GDM patients and 61.6% of the T1DM participants, while only 28.6% of the normal pregnancy patients experienced a calcium deficiency. The highest incidence of inadequate intake in each of the GDM, T1DM and control groups was observed for vitamin D (100%, 100%, 100%), folate (97.7%, 100%, 100%), iron (97.7%, 100%, 100%), and iodine (97.7%, 92.4%, 85.7%), respectively.Conclusions: Diet alone may not be enough to provide adequate levels of vitamins and minerals for most micronutrients. Supplement use reduces the risk of inadequate intake for many micronutrients, but diet-related issues during pregnancy and pregnancy diagnosed with diabetes remain, and they deserve to be addressed during public health interventions
acute cocaine treatment enhances the antagonistic allosteric adenosine a2a dopamine d2 receptor receptor interactions in rat dorsal striatum without increasing significantly extracellular dopamine levels
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Association between rs7901695 and rs7903146 polymorphisms of the TCF7L2 gene and gestational diabetes in the population of Southern Poland
Objectives: The etiology of gestational diabetes mellitus (GDM) remains to be fully elucidated. Elevated risk for type 2 diabetes in patients with history of GDM and for GDM in women with familial history of diabetes may suggest that GDM and type 2 diabetes share a common genetic and environmental background. The TCF7L2 (Transcription Factor 7 Like 2) gene is one of the most important genetic factors of the established correlation with type 2 diabetes, and it may also play a role in the pathophysiology of GDM.The aim of the study was to assess the influence of two polymorphisms of the TCF7L2 gene (rs7901695 and rs7903146), which are associated with the development of type 2 diabetes, in women with GDM.Material and methods: The study included 50 women with glucose tolerance disorders diagnosed for the first time during the current pregnancy. Single nucleotide polymorphisms (SNPs) were genotyped using allelic discrimination. The results were confirmed using the sequencing method. Selected clinical parameters were also analyzed.Results: No correlation between the studied polymorphisms of the TCF7L2 gene and GDM was observed. Glycemic control with diet or diet and insulin was associated with better control of the weight gain during pregnancy.Conclusions: No correlation between rs7903146 and rs7901695 polymorphisms of the TCF7L2 gene and GDM was found. Glycemic control with diet or diet and insulin is associated with better control of the weight gain during pregnancy
TP53 polymorphism in plasma cell myeloma
Introduction. Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients.
Material and methods. Genomic DNA from newly diagnosed 59 patients (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of 40 PCM patients were treated with bortezomib (1, 2 and 4 nM).
Results. The P allele of the P72R polymorphism was more common than the R allele in PMC patients compared to controls (39% vs. 24%), and the difference was significant (p = 0.02). The PP and PR genotypes (in combinaÂtion) were more frequent among cases than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level and 2 nM bortezomib concentration the PP genotype was associated with higher necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed in patients with the PP genotype compared to patients with the PR or RR genotypes (20 months) (p = 0.04).
Conclusions. The results suggest that P72R polymorphisms may be associated with an increased PCM risk and may affect OS of PCM patients. However, we saw no consistent results of the polymorphism effect on apoptosis and necrosis in cell cultures derived from PCM patients. Further studies are need in this regard
Gene expression profile comparison between bone metastatic and non-metastatic prostate cancer cell lines
Astronauts suffer from cardiovascular deconditioning during space flight where they are exposed to microgravity. Alterations under real and simulated microgravity have been found e.g. in the cytoskeleton and apoptosis in endothelial cells (ECs) and smooth muscle cells (SMCs)1, 2. P2 receptors play an important role in a variety of vascular functions of ECs and SMCs. However, the functional role of purinergic signalling in ECs and SMCs under microgravity is still unclear.
In this study primary ECs and SMCs were isolated from bovine aorta and characterized using specific markers. Additionally, EC growth medium collected during culture under normal gravity was used as conditioned medium for SMCs and vice versa to mimic a co-culture model. Here we show for the first time that the P2-receptor expression pattern is altered in ECs and SMCs under simulated microgravity achieved by a clinostat. Interestingly, conditioned medium compensated the alterations in the expression of specific P2-receptors. P2X7 was down-regulated in ECs after 24h clinorotation but recovered to the gene and protein expression level found under normal gravity when cultured in conditioned medium from SMCs.
Our results showed an altered P2-receptor expression pattern under simulated microgravity. The paracrine effect between ECs and SMCs seems to be an important regulator of cell behaviour under altered gravity conditions. Several artificial P2-receptor ligands are already utilized as drugs. Thus it might be reasonable to consider them for drug development for astronaut treatment of cardiovascular deconditioning in the future
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